Cancer–testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors.
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
This study compared the expression of E-cadherin, β-catenin, and MUC1 in multicentric/multifocal breast cancers versus unifocal breast cancers of identical tumor size and grade. The study found significantly downregulated expression of E-cadherin in multicentric/multifocal cancers compared to unifocal cancers. In contrast, no significant differences were seen in β-catenin expression between the two groups. Within the unifocal group, E-cadherin and β-catenin expression were positively correlated, but this was not seen in the multicentric/multifocal group. The results suggest multicentric/multifocal and unifocal breast cancers differ in E-
This document summarizes the current immunotherapy and targeted therapy options for endometrial cancer. It discusses the biological and genetic background of endometrial cancer and its classification into types. The main immunotherapeutic options available include anti-cancer vaccines, immune checkpoint inhibitors that target molecules like PD-1 and PD-L1, and adoptive cell therapies. Several clinical trials of these therapies for endometrial cancer are ongoing based on their success in other cancer types. Identification of genetic alterations in endometrial cancer is leading to new targeted therapy options.
This document summarizes research targeting metastatic triple negative breast cancer using phage display nanotechnology. Key points:
- Triple negative breast cancer, which lacks estrogen, progesterone and HER2 receptors, has poor survival rates and few treatment options. The goal is to target cancer stem cells that initiate metastases.
- Phage display was used to select peptide sequences that bind specifically to triple negative breast cancer cells. Over 3 rounds of selection and amplification, binding peptides were increasingly enriched.
- Isolated phage clones were sequenced to identify binding peptide sequences for further development of targeted nanomedicines to treat metastatic triple negative breast cancer. Future work will modify pre-existing cancer nanomedicines with the selected peptides.
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Tri...UCLA
The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.
This retrospective study analyzed 54 Hispanic patients in Puerto Rico with triple-negative breast cancer (TNBC). The median age was 55 years and most patients presented with early stage disease. Factors associated with poorer progression-free survival included lymph node involvement, tumor size over 2 cm, and stage IV disease. The 5-year overall and progression-free survival rates were 81% and 80% respectively, similar to rates reported for other populations. The results suggest that differences in TNBC outcomes between Hispanic and non-Hispanic women may be due to socioeconomic factors rather than biological differences.
Immunotherapy is based in reactivating the patient immune system specifically against the neoplasia, tumors have immunosuppression mechanisms that allow them to control and evade the immune response.
There are different immunotherapy approaches like tumor-targeting monoclonal antibodies, adoptive T cell transfer, anticancer vaccines, checkpoint inhibitors, most of these in important clinical trials in which the effects and toxicities are still evaluated. They are also beginning tested on a combination of immunotherapies and other non-immunological therapies in order to increase the survival of patients. Immunotherapy is still a young area and it needs to reach its peak, but it will surely be a great tool to treat and cure cancer.
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
This study compared the expression of E-cadherin, β-catenin, and MUC1 in multicentric/multifocal breast cancers versus unifocal breast cancers of identical tumor size and grade. The study found significantly downregulated expression of E-cadherin in multicentric/multifocal cancers compared to unifocal cancers. In contrast, no significant differences were seen in β-catenin expression between the two groups. Within the unifocal group, E-cadherin and β-catenin expression were positively correlated, but this was not seen in the multicentric/multifocal group. The results suggest multicentric/multifocal and unifocal breast cancers differ in E-
This document summarizes the current immunotherapy and targeted therapy options for endometrial cancer. It discusses the biological and genetic background of endometrial cancer and its classification into types. The main immunotherapeutic options available include anti-cancer vaccines, immune checkpoint inhibitors that target molecules like PD-1 and PD-L1, and adoptive cell therapies. Several clinical trials of these therapies for endometrial cancer are ongoing based on their success in other cancer types. Identification of genetic alterations in endometrial cancer is leading to new targeted therapy options.
This document summarizes research targeting metastatic triple negative breast cancer using phage display nanotechnology. Key points:
- Triple negative breast cancer, which lacks estrogen, progesterone and HER2 receptors, has poor survival rates and few treatment options. The goal is to target cancer stem cells that initiate metastases.
- Phage display was used to select peptide sequences that bind specifically to triple negative breast cancer cells. Over 3 rounds of selection and amplification, binding peptides were increasingly enriched.
- Isolated phage clones were sequenced to identify binding peptide sequences for further development of targeted nanomedicines to treat metastatic triple negative breast cancer. Future work will modify pre-existing cancer nanomedicines with the selected peptides.
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Tri...UCLA
The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.
This retrospective study analyzed 54 Hispanic patients in Puerto Rico with triple-negative breast cancer (TNBC). The median age was 55 years and most patients presented with early stage disease. Factors associated with poorer progression-free survival included lymph node involvement, tumor size over 2 cm, and stage IV disease. The 5-year overall and progression-free survival rates were 81% and 80% respectively, similar to rates reported for other populations. The results suggest that differences in TNBC outcomes between Hispanic and non-Hispanic women may be due to socioeconomic factors rather than biological differences.
Immunotherapy is based in reactivating the patient immune system specifically against the neoplasia, tumors have immunosuppression mechanisms that allow them to control and evade the immune response.
There are different immunotherapy approaches like tumor-targeting monoclonal antibodies, adoptive T cell transfer, anticancer vaccines, checkpoint inhibitors, most of these in important clinical trials in which the effects and toxicities are still evaluated. They are also beginning tested on a combination of immunotherapies and other non-immunological therapies in order to increase the survival of patients. Immunotherapy is still a young area and it needs to reach its peak, but it will surely be a great tool to treat and cure cancer.
Global cancer immunotherapy market outlook 2020KuicK Research
The document provides an overview of the global cancer immunotherapy market outlook for 2020. It discusses how cancer immunotherapies work by modulating the immune system to treat cancer. The market has seen significant growth with many approved and pipeline immunotherapies across classes like monoclonal antibodies, cytokines, vaccines, and immune checkpoint inhibitors. The market is expected to continue growing in coming years due to increased research and funding leading to new treatment modalities and biomarkers to expand the use of immunotherapies for additional cancer types.
Prognostic & predictive factors of breast cancerMohammed Fathy
1) Prognostic factors provide information about a patient's outcome without treatment, while predictive factors provide information about how a patient may respond to a specific treatment.
2) Many clinical factors, pathological features, tissue markers, and genomic expression profiles can provide prognostic and predictive information for breast cancer patients.
3) Key prognostic factors include age, tumor stage, tumor size, nodal involvement, histological grade, hormone receptor status, and intrinsic subtypes. Predictive factors include hormone receptor and HER2 status.
Zauderer, M.G., et al. Clinical Cancer Research, 2017.sellasq4
1. This randomized phase II trial evaluated the WT1 peptide vaccine galinpepimut-S combined with GM-CSF and Montanide in patients with malignant pleural mesothelioma after multimodality therapy.
2. The trial randomized 41 patients to galinpepimut-S plus adjuvants or adjuvants alone. The control arm was stopped early due to a futility analysis showing progression within 1 year in over 10 of the first 20 patients.
3. Trends toward improved progression-free survival (10.1 vs 7.4 months) and overall survival (22.8 vs 18.3 months) were observed in the vaccine arm compared to control, but the trial was
Low expression of the X-linked ribosomal protein S4 in human serous epithelia...Enrique Moreno Gonzalez
The X-linked ribosomal protein S4 (RPS4X), which is involved in cellular translation and proliferation, has previously been identified as a partner of the overexpressed multifunctional protein YB-1 in several breast cancer cells. Depletion of RPS4X results in consistent resistance to cisplatin in such cell lines.
1. The study aimed to validate immunohistochemical (IHC) surrogates for intrinsic breast cancer subtypes identified by gene expression profiling, using the PAM50 assay as the gold standard.
2. Among 46 biomarkers tested by IHC on a tissue microarray, loss of INPP4B expression showed the best combination of sensitivity (61.1%) and specificity (98.6%) for basal-like breast cancer defined by PAM50.
3. Nestin positivity also strongly correlated with basal-like subtype, consistent with other studies, and may be a useful positive basal marker. A multi-marker IHC panel may better define basal-like breast cancer than single biomarkers.
“Cancer Immunotherapy Market & Clinical Pipeline Insight” Report Highlights:
Cancer Immunotherapy Market Overview
Cancer Immunotherapy Market Dynamics
Cancer Immunotherapy Pipeline: 1080 Drug in Clinical Pipeline
Cancer Monoclonal Antibodies Clinical Pipeline by Phase & Country
Cancer Vaccine Clinical Pipeline by Phase & Country
Oncolytic Viruses Clinical Pipeline by Phase & Country
Cancer Cytokine Therapy Clinical Trial Insight by Phase & Country
Cancer Cell Therapy Clinical Trial Insight by Phase & Country
Currently there are 605 Cancer Monoclonal Antibodies, 289 Cancer Vaccines, 40 Oncolytic Viruses Drugs, 64 Cytokines Therapies & 82 Cell Therapies are in Clinical Pipeline.
Potential of Targeting Bone Metastases with Immunotherapies_Crimson PublishersCrimsonpublishersCancer
Potential of Targeting Bone Metastases with Immunotherapies
Bone metastases are common in many cancers and result in low survival rates. Immunotherapies have shown promise in treating some patients with bone metastases. Case reports have shown individual patients experiencing decreased bone lesion growth or complete remission of bone metastases using immunotherapies targeting PD-1, PD-L1, or CTLA-4. However, immunotherapies may also cause harmful skeletal effects like fractures or spinal cord compression. Further research is still needed to determine if immunotherapies are effective against bone metastases in large patient groups and to understand their potential skeletal side effects.
This study aims to evaluate the gene expression profile of FOXE1 mRNA in paired thyroid tumor and non-tumor tissue samples. Preliminary results from the first 10 paired samples show variation in FOXE1 gene expression levels between tumor and non-tumor tissues, with non-tumor tissue appearing to have higher FOXE1 expression compared to tumor tissue. Analysis of more sample pairs is ongoing, and FOXE1 expression levels will be compared to patient clinical data and tumor pathological characteristics. The results so far indicate there may be a profile of FOXE1 expression in thyroid cancer.
This document provides an overview of immunotherapy for cancer treatment. It discusses how the immune system normally protects the body from cancer but can fail to control cancer cells. Various immunotherapy strategies are described to harness the immune system against cancer, including improving antigen presentation to prime more immune cells. The history and types of cancer immunotherapy are reviewed, as well as how immunotherapy works, common approaches, effectiveness, and potential risks. Current research focuses on continuing to develop more effective immunotherapy treatments for cancer.
This document discusses how the Cancer Genome Atlas (TCGA) project, which aimed to sequence tumors to identify genetic changes and develop treatments, is now at a crossroads due to the confounding factor of intratumoral heterogeneity. Sequencing more tumors with single biopsies cannot capture heterogeneity between tumor parts or over time. Obtaining multiple biopsies presents logistical challenges. Recent studies reveal significant genetic differences within individual tumors in space and time. This challenges the utility of TCGA's approach and whether its data can guide treatment. Better methods are needed to address tumor heterogeneity.
Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovari...ijtsrd
MSC CM suppresses epithelial ovarian cancer cells in vitro in a concentration-dependent manner. When ovarian cancer cells were treated with MSC CM at concentrations of 100%, 75%, 50%, and 25% for 72 hours, cell morphology changes were observed including cell shrinkage, debris and reduced cell numbers compared to control. MTT assays showed reduced proliferation and Annexin V testing demonstrated increased early and late apoptosis. Cell cycle analysis found an increased sub-G1 phase, indicating apoptosis. Expression of embryonic stemness genes was also progressively suppressed in cancer cells treated with MSC CM compared to control. Therefore, MSC CM has potential as an ovarian cancer inhibitor by creating new treatment modalities.
This document summarizes a study that used DNA microarrays to analyze gene expression patterns in ovarian carcinomas. The key findings include:
1) The study identified groups of genes that distinguished clear cell ovarian carcinomas from other subtypes, and low-grade from high-grade serous papillary carcinomas.
2) Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas based on their gene expression patterns.
3) A comparison of ovarian carcinomas to breast cancers revealed 62 genes that correctly classified all 125 specimens, with genes like PAX8, mesothelin, and ephrin-B1 more highly expressed in ovarian carcinomas.
This document summarizes two recent studies on ovarian cancer published in PLoS Medicine. The first study found that biomarkers for ovarian cancer are more strongly associated with histological subtypes than disease stage, suggesting molecular profiling may be needed to properly classify and manage different subtypes. The second study identified an 86-gene expression profile from tumor samples that predicts survival outcomes in patients with advanced ovarian cancer. Validation in independent studies is still needed, but the findings provide encouraging progress in developing prognostic markers and molecular signatures to help guide personalized treatment of ovarian cancer.
This document discusses cancer and provides information about its causes, global burden, history, development process, genetics, types like breast cancer, research areas, and molecular targets for treatment. It notes that cancer is caused by both environmental and genetic factors. While over 80% of cancers are due to nature like radiation and viruses, under 10% are due to nurture or genes. The global cancer burden is outlined and breast cancer is used as a paradigm to discuss heterogeneous subtypes including luminal A, luminal B, basal-like, and ERBB2+ based on molecular profiles and markers. Future work is needed to better integrate molecular and clinical classification of cancers like breast cancer to improve diagnosis, treatment and prognosis.
The document discusses molecular testing for breast cancer. It describes how molecular testing can provide insights into breast cancer subtypes, predict response to treatments, and assess recurrence risk. Several molecular tests are discussed, including Oncotype DX, Mammaprint, Prosigna, and tumor sequencing to identify actionable mutations. Molecular profiling is becoming increasingly important for personalized prevention, diagnosis, and treatment of breast cancer.
1) Researchers have discovered a new genetic test using mitochondrial genes that can more accurately predict cancer recurrence than current methods. The test analyzes over 400 mitochondrial genes and certain genes were found to predict recurrence up to 5 times higher.
2) Genetics provides an understanding of the biological composition of humans and pathological processes. It involves studying gene mapping, inheritance of diseases, and molecular mechanisms of how genes cause disorders. This knowledge aids in diagnosis and treatment.
3) A study used genome editing to block a gene, OCT4, that is important for early human embryo development. This revealed the gene is necessary for proper formation of the blastocyst. Understanding key genes needed for embryo development could improve IVF treatments and shed
How patient subpopulations are changing the commercialization of oncology pro...IMSHealthRWES
An excerpt from the latest issue of AccessPoint, looking at how genomic profiling data is transforming our understanding of patient subpopulations - a key to targeting treatments with greater precision
This document summarizes recent advances in immunotherapy for solid tumors. It discusses how immunotherapy has established itself as an effective treatment strategy, building on William Coley's pioneering work in the late 1800s using bacteria to elicit anti-tumor immune responses. The document outlines several key immunotherapy approaches, including immune checkpoint inhibitors, adoptive cellular therapy, strategies to enhance tumor immunogenicity like radiotherapy and oncolytic viruses, and cancer vaccines. It also discusses how tumor-infiltrating lymphocytes and immunoscore can help predict cancer prognosis and how the immune system interacts with tumors.
Global cancer immunotherapy market outlook 2020KuicK Research
The document provides an overview of the global cancer immunotherapy market outlook for 2020. It discusses how cancer immunotherapies work by modulating the immune system to treat cancer. The market has seen significant growth with many approved and pipeline immunotherapies across classes like monoclonal antibodies, cytokines, vaccines, and immune checkpoint inhibitors. The market is expected to continue growing in coming years due to increased research and funding leading to new treatment modalities and biomarkers to expand the use of immunotherapies for additional cancer types.
Prognostic & predictive factors of breast cancerMohammed Fathy
1) Prognostic factors provide information about a patient's outcome without treatment, while predictive factors provide information about how a patient may respond to a specific treatment.
2) Many clinical factors, pathological features, tissue markers, and genomic expression profiles can provide prognostic and predictive information for breast cancer patients.
3) Key prognostic factors include age, tumor stage, tumor size, nodal involvement, histological grade, hormone receptor status, and intrinsic subtypes. Predictive factors include hormone receptor and HER2 status.
Zauderer, M.G., et al. Clinical Cancer Research, 2017.sellasq4
1. This randomized phase II trial evaluated the WT1 peptide vaccine galinpepimut-S combined with GM-CSF and Montanide in patients with malignant pleural mesothelioma after multimodality therapy.
2. The trial randomized 41 patients to galinpepimut-S plus adjuvants or adjuvants alone. The control arm was stopped early due to a futility analysis showing progression within 1 year in over 10 of the first 20 patients.
3. Trends toward improved progression-free survival (10.1 vs 7.4 months) and overall survival (22.8 vs 18.3 months) were observed in the vaccine arm compared to control, but the trial was
Low expression of the X-linked ribosomal protein S4 in human serous epithelia...Enrique Moreno Gonzalez
The X-linked ribosomal protein S4 (RPS4X), which is involved in cellular translation and proliferation, has previously been identified as a partner of the overexpressed multifunctional protein YB-1 in several breast cancer cells. Depletion of RPS4X results in consistent resistance to cisplatin in such cell lines.
1. The study aimed to validate immunohistochemical (IHC) surrogates for intrinsic breast cancer subtypes identified by gene expression profiling, using the PAM50 assay as the gold standard.
2. Among 46 biomarkers tested by IHC on a tissue microarray, loss of INPP4B expression showed the best combination of sensitivity (61.1%) and specificity (98.6%) for basal-like breast cancer defined by PAM50.
3. Nestin positivity also strongly correlated with basal-like subtype, consistent with other studies, and may be a useful positive basal marker. A multi-marker IHC panel may better define basal-like breast cancer than single biomarkers.
“Cancer Immunotherapy Market & Clinical Pipeline Insight” Report Highlights:
Cancer Immunotherapy Market Overview
Cancer Immunotherapy Market Dynamics
Cancer Immunotherapy Pipeline: 1080 Drug in Clinical Pipeline
Cancer Monoclonal Antibodies Clinical Pipeline by Phase & Country
Cancer Vaccine Clinical Pipeline by Phase & Country
Oncolytic Viruses Clinical Pipeline by Phase & Country
Cancer Cytokine Therapy Clinical Trial Insight by Phase & Country
Cancer Cell Therapy Clinical Trial Insight by Phase & Country
Currently there are 605 Cancer Monoclonal Antibodies, 289 Cancer Vaccines, 40 Oncolytic Viruses Drugs, 64 Cytokines Therapies & 82 Cell Therapies are in Clinical Pipeline.
Potential of Targeting Bone Metastases with Immunotherapies_Crimson PublishersCrimsonpublishersCancer
Potential of Targeting Bone Metastases with Immunotherapies
Bone metastases are common in many cancers and result in low survival rates. Immunotherapies have shown promise in treating some patients with bone metastases. Case reports have shown individual patients experiencing decreased bone lesion growth or complete remission of bone metastases using immunotherapies targeting PD-1, PD-L1, or CTLA-4. However, immunotherapies may also cause harmful skeletal effects like fractures or spinal cord compression. Further research is still needed to determine if immunotherapies are effective against bone metastases in large patient groups and to understand their potential skeletal side effects.
This study aims to evaluate the gene expression profile of FOXE1 mRNA in paired thyroid tumor and non-tumor tissue samples. Preliminary results from the first 10 paired samples show variation in FOXE1 gene expression levels between tumor and non-tumor tissues, with non-tumor tissue appearing to have higher FOXE1 expression compared to tumor tissue. Analysis of more sample pairs is ongoing, and FOXE1 expression levels will be compared to patient clinical data and tumor pathological characteristics. The results so far indicate there may be a profile of FOXE1 expression in thyroid cancer.
This document provides an overview of immunotherapy for cancer treatment. It discusses how the immune system normally protects the body from cancer but can fail to control cancer cells. Various immunotherapy strategies are described to harness the immune system against cancer, including improving antigen presentation to prime more immune cells. The history and types of cancer immunotherapy are reviewed, as well as how immunotherapy works, common approaches, effectiveness, and potential risks. Current research focuses on continuing to develop more effective immunotherapy treatments for cancer.
This document discusses how the Cancer Genome Atlas (TCGA) project, which aimed to sequence tumors to identify genetic changes and develop treatments, is now at a crossroads due to the confounding factor of intratumoral heterogeneity. Sequencing more tumors with single biopsies cannot capture heterogeneity between tumor parts or over time. Obtaining multiple biopsies presents logistical challenges. Recent studies reveal significant genetic differences within individual tumors in space and time. This challenges the utility of TCGA's approach and whether its data can guide treatment. Better methods are needed to address tumor heterogeneity.
Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovari...ijtsrd
MSC CM suppresses epithelial ovarian cancer cells in vitro in a concentration-dependent manner. When ovarian cancer cells were treated with MSC CM at concentrations of 100%, 75%, 50%, and 25% for 72 hours, cell morphology changes were observed including cell shrinkage, debris and reduced cell numbers compared to control. MTT assays showed reduced proliferation and Annexin V testing demonstrated increased early and late apoptosis. Cell cycle analysis found an increased sub-G1 phase, indicating apoptosis. Expression of embryonic stemness genes was also progressively suppressed in cancer cells treated with MSC CM compared to control. Therefore, MSC CM has potential as an ovarian cancer inhibitor by creating new treatment modalities.
This document summarizes a study that used DNA microarrays to analyze gene expression patterns in ovarian carcinomas. The key findings include:
1) The study identified groups of genes that distinguished clear cell ovarian carcinomas from other subtypes, and low-grade from high-grade serous papillary carcinomas.
2) Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas based on their gene expression patterns.
3) A comparison of ovarian carcinomas to breast cancers revealed 62 genes that correctly classified all 125 specimens, with genes like PAX8, mesothelin, and ephrin-B1 more highly expressed in ovarian carcinomas.
This document summarizes two recent studies on ovarian cancer published in PLoS Medicine. The first study found that biomarkers for ovarian cancer are more strongly associated with histological subtypes than disease stage, suggesting molecular profiling may be needed to properly classify and manage different subtypes. The second study identified an 86-gene expression profile from tumor samples that predicts survival outcomes in patients with advanced ovarian cancer. Validation in independent studies is still needed, but the findings provide encouraging progress in developing prognostic markers and molecular signatures to help guide personalized treatment of ovarian cancer.
This document discusses cancer and provides information about its causes, global burden, history, development process, genetics, types like breast cancer, research areas, and molecular targets for treatment. It notes that cancer is caused by both environmental and genetic factors. While over 80% of cancers are due to nature like radiation and viruses, under 10% are due to nurture or genes. The global cancer burden is outlined and breast cancer is used as a paradigm to discuss heterogeneous subtypes including luminal A, luminal B, basal-like, and ERBB2+ based on molecular profiles and markers. Future work is needed to better integrate molecular and clinical classification of cancers like breast cancer to improve diagnosis, treatment and prognosis.
The document discusses molecular testing for breast cancer. It describes how molecular testing can provide insights into breast cancer subtypes, predict response to treatments, and assess recurrence risk. Several molecular tests are discussed, including Oncotype DX, Mammaprint, Prosigna, and tumor sequencing to identify actionable mutations. Molecular profiling is becoming increasingly important for personalized prevention, diagnosis, and treatment of breast cancer.
1) Researchers have discovered a new genetic test using mitochondrial genes that can more accurately predict cancer recurrence than current methods. The test analyzes over 400 mitochondrial genes and certain genes were found to predict recurrence up to 5 times higher.
2) Genetics provides an understanding of the biological composition of humans and pathological processes. It involves studying gene mapping, inheritance of diseases, and molecular mechanisms of how genes cause disorders. This knowledge aids in diagnosis and treatment.
3) A study used genome editing to block a gene, OCT4, that is important for early human embryo development. This revealed the gene is necessary for proper formation of the blastocyst. Understanding key genes needed for embryo development could improve IVF treatments and shed
How patient subpopulations are changing the commercialization of oncology pro...IMSHealthRWES
An excerpt from the latest issue of AccessPoint, looking at how genomic profiling data is transforming our understanding of patient subpopulations - a key to targeting treatments with greater precision
This document summarizes recent advances in immunotherapy for solid tumors. It discusses how immunotherapy has established itself as an effective treatment strategy, building on William Coley's pioneering work in the late 1800s using bacteria to elicit anti-tumor immune responses. The document outlines several key immunotherapy approaches, including immune checkpoint inhibitors, adoptive cellular therapy, strategies to enhance tumor immunogenicity like radiotherapy and oncolytic viruses, and cancer vaccines. It also discusses how tumor-infiltrating lymphocytes and immunoscore can help predict cancer prognosis and how the immune system interacts with tumors.
This document summarizes a literature review on intra-tumoral lymphocytes (TIL) in breast cancer. The review found that assessing TIL is unnecessary in high-grade tumors but may be useful in intermediate-grade tumors. In neoadjuvant and adjuvant settings, CD3+ lymphocytes correlate with better response to chemotherapy. After chemotherapy, quantifying regulatory T cells (Treg; CD4+FOXP3+) is helpful as decreased levels correlate with better prognosis. While the role of TIL in breast cancer is established, the optimal methods for microscopic assessment and immunohistochemical subtyping of TIL remain unclear.
Cancer stem cells (CSCs) are a subset of cells found in tumors that can self-renew and differentiate, leading to tumor growth, recurrence, and metastasis. In contrast to normal stem cells, CSCs have mutations that allow uncontrolled growth and resistance to chemotherapy and radiation. Immunocellular Therapeutics' dendritic cell-based vaccine ICT-107 targets multiple CSC antigens to activate the immune system against brain cancer cells. Phase I/II trials showed ICT-107 increased survival rates and time to tumor progression compared to standard treatments.
This white paper discusses improving the clinical development of cancer immunotherapies. It outlines the current immunotherapy landscape including checkpoint inhibitors, adoptive T cell therapies, cancer vaccines, and biomarkers. The paper emphasizes that while immunotherapy has promising results for some patients and cancer types, more research is needed to understand which patients will benefit most from which approaches and how to best leverage various immune system components in the fight against cancer. Operational considerations and cautions for clinical development are also discussed.
The document discusses molecular subtyping of breast cancer through gene expression profiling which has identified major subtypes including luminal A, luminal B, HER2-enriched, and basal-like. It describes the characteristic gene expressions and clinical features of each subtype. Molecular subtyping is shown to have prognostic and predictive relevance for breast cancer outcomes and treatment responses.
This article discusses recent advances in understanding the immune system's response to cancer. It identifies three key points:
1) Tumor antigens that the immune system can recognize have been identified, including molecules that are unique to cancer cells (tumor-specific) and molecules expressed differently by cancer and normal cells (tumor-associated). Over 100 peptides have been identified, some from unique mutations and most from proteins differentially expressed in tumors.
2) Cancers can elicit inflammatory responses through danger signals and tumor antigens, supporting the concept of "immunosurveillance" where the immune system recognizes and eliminates malignant cells. However, tumors can also suppress immunity through mechanisms like regulatory T cells and immunosuppressive enzymes.
This intro is geared towards interested novices who wish to find a resource that can serve as a starting point for further self-study. This is not meant to replace a doctor's advice. Please approach a medical professional for any health condition.
This document reviews emerging biomarkers and technologies for personalized cancer immunotherapy. It discusses how our understanding of the immune system's role in cancer has evolved over the last century. Checkpoint blockade therapies have shown success in treating some cancers, but biomarkers are still needed to identify which patients will benefit and experience fewer side effects. The document explores biomarkers for CTLA-4 blockade and the PD-1/PD-L1 axis. It also discusses novel technologies that could help discover new biomarkers and advance precision medicine in cancer immunotherapy.
Claudin 1 expression in basal-like breast cancer is related to patient ageEnrique Moreno Gonzalez
Defects in tight junctions, gate-keepers of the integrity of the epidermal barrier function, are known to contribute to cancer development. As such, enhancing our understanding of how the expression of proteins involved in these junctions is regulated in cancer, remains a priority. Although the expression of one of these proteins, claudin 1, is down regulated in most invasive human breast cancers (HBC), we have recently shown that high levels of claudin 1, characterized tumors belonging to the very aggressive basal-like breast cancer (BLBC) subtype. In these tumors, the claudin 1.
The document provides guidelines for the treatment of breast cancer. It discusses the rising incidence of breast cancer in the US but declining mortality, suggesting benefits from early detection and treatment. It then covers breast cancer risk factors, staging, pathology assessment, treatment approaches, and treatment options for specific breast cancer stages and types. The guidelines are intended to help clinicians provide high-quality, evidence-based care for their breast cancer patients.
Nuclear TK1 expression is an independent prognostic factor for survival in pr...Enrique Moreno Gonzalez
TK1 expression was determined by immunohistochemistry in cervical lesions (cervical intraepithelial neoplasia (CIN), n = 216; invasive cervical carcinoma, n = 84). TK1 and Ki-67
expressions and pathological/FIGO stages and age were correlated with 5-year survival by Kaplan-Meier, log rank and COX hazard uni- and multivariate analyses.
Primary small cell breast carcinoma represents less than 1% of breast cancers. Due to its rarity, there are no uniformly accepted guidelines for treatment. Its prognosis is varied being generally regarded as worse than that of most breast cancers and it poses unique diagnostic challenges. We present a case of primary small cell breast cancer, rationale for our management strategies with reference to the published literature to serve as a guide to the management of this rare cancer of the breast.
Neoadjuvant rh-endostatin, docetaxel and epirubicin for breast cancer: effica...Enrique Moreno Gonzalez
This document summarizes a prospective, randomized, phase II clinical trial that evaluated the efficacy and safety of neoadjuvant chemotherapy with or without rh-endostatin for breast cancer. 68 patients received either 3 cycles of docetaxel and epirubicin (DE) chemotherapy alone or DE chemotherapy combined with rh-endostatin. The combination therapy showed a higher objective response rate of 91% compared to 68% for chemotherapy alone, with more complete responses but no increase in adverse effects. The combination appeared to work better in premenopausal patients and those with better performance status.
The document discusses the role of immunity in tumor surveillance and elimination. It describes the three phases of tumor immunoediting: elimination, equilibrium, and escape. In the elimination phase, the immune system detects and destroys nascent tumor cells through immune cells like NK cells and CD4/CD8 T cells. During equilibrium, tumor cells evolve under immune selective pressure. Eventually tumor variants emerge that can evade the immune system, entering the escape phase where immune-mediated destruction fails and tumors grow progressively. Evidence from mouse models supports the concept that both innate and adaptive immunity play roles in preventing tumor development. A better understanding of immunoediting could help improve cancer immunotherapy approaches.
Engineered T Cell Therapy for
Gynecologic Malignancies
Challenges and Opportu...RudrikaChandra1
This document discusses engineered T cell therapy for gynecologic malignancies. It begins by introducing common gynecologic cancers and recent successes of adoptive T cell therapy using engineered T cells for other cancers. The document then summarizes two main types of engineered T cells - T cell receptor modified T cells (TCR-Ts) and chimeric antigen receptor T cells (CAR-Ts) - and their mechanisms of action. Finally, it explores opportunities to apply these engineered T cell therapies to treat gynecologic cancers based on preclinical research and early clinical trials.
This document describes the characterization of a new head and neck squamous cell carcinoma (HNSCC) cell line called USC-HN2. USC-HN2 was established from a patient with recurrent oral cavity cancer. Characterization showed USC-HN2 has properties typical of aggressive oral HNSCC, including expression of markers like EGFR, CD44v6, and FABP5. Testing revealed USC-HN2 strongly induces regulatory T cells and myeloid-derived suppressor cells in vitro, suggesting an immunosuppressive phenotype. Comparison to another HNSCC cell line, SCCL-MT1, showed both lines have robust cytokine production and immune cell induction, making them useful models for
1) Identification of gene signatures and biomarkers in breast cancer, such as the Notch pathway, may help develop targeted therapies for different subtypes. 2) The Notch pathway promotes breast cancer stem cell growth and inhibiting it with gamma secretase inhibitors reduces cancer cell proliferation and invasion. 3) PARP inhibitors show promise as a targeted treatment for triple negative breast cancer associated with BRCA mutations by exploiting "synthetic lethality" - inhibiting both BRCA and PARP pathways kills cancer cells. Large-scale identification of PARP substrates may help identify predictive markers for effective PARP inhibitor therapy.
Similar to Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications (20)
Gene expression analysis of a Helicobacter pyloriinfected and high-salt diet-...Enrique Moreno Gonzalez
Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model.
Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
Differences in microRNA expression during tumor development in the transition...Enrique Moreno Gonzalez
The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.
The life in sight application study (LISA): design of a randomized controlled...Enrique Moreno Gonzalez
It is widely recognized that spiritual care plays an important role in physical and psychosocial well-being of cancer patients, but there is little evidence based research on the effects of spiritual care. We will conduct a randomized controlled trial on spiritual care using a brief structured interview scheme supported by an e-application. The aim is to examine whether an assisted reflection on life events and ultimate life goals can improve quality of life of cancer patients.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
Assessment of preoperative exercise capacity in hepatocellular carcinoma pati...Enrique Moreno Gonzalez
Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy.
Overexpression of YAP 1 contributes to progressive features and poor prognosi...Enrique Moreno Gonzalez
Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.
CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1a...Enrique Moreno Gonzalez
Glioblastomas, the most common and malignant brain tumors of the central nervous system, exhibit high invasive capacity, which hinders effective therapy. Therefore, intense efforts aimed at improved therapeutics are ongoing to delineate the molecular mechanisms governing glioma cell migration and invasion.
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.
Differentiation of irradiation and cetuximab induced skin reactions in patien...Enrique Moreno Gonzalez
In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before.
Cholestasis induces reversible accumulation of periplakin in mouse liverEnrique Moreno Gonzalez
Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in noncutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis.
Functional p53 is required for rapid restoration of daunorubicin-induced lesi...Enrique Moreno Gonzalez
This document summarizes a research article that studied the role of p53 in daunorubicin (DNR)-induced lesions in the spleen. The key findings were:
1) DNR treatment caused more rapid cell death and weight loss in the spleens of wild type mice compared to p53-null mice.
2) While wild type mouse spleens recovered normal morphology 8 days after DNR treatment, p53-null mouse spleens still had large necrotic lesions.
3) DNR treatment increased p21 levels in wild type mice but not p53-null mice, indicating p53 is required for p21 induction.
4) The results suggest p53
Post-diagnosis hemoglobin change associates with overall survival of multiple...Enrique Moreno Gonzalez
Anemia refers to low hemoglobin (Hb) level and is a risk factor of cancer patient survival. The National Comprehensive Cancer Network recently suggested that post-diagnosis Hb change, regardless of baseline Hb level, indicates the potential presence of anemia. However, there is no epidemiological study evaluating whether Hb change has direct prognostic values for cancer patients at the population level.
Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation car...Enrique Moreno Gonzalez
Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Enrique Moreno Gonzalez
Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial β-oxidation. In this study we assessed mitochondrial β-oxidation in CH-C patients by investigating ketogenesis during fasting.
Intraepithelial lymphocyte distribution differs between the bulb and the seco...Enrique Moreno Gonzalez
Evaluation of intraepithelial duodenal lymphocytosis (IDL) is important in celiac disease (CD). There is no established cut-off value for increased number of IELs in the bulb. We therefore investigated the relation between IEL counts in the bulb and duodenal specimens in non-celiac subjects.
Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on...Enrique Moreno Gonzalez
Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics.
Association between variations in the fat mass and obesity-associated gene an...Enrique Moreno Gonzalez
It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk.
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
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- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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Mercurius is named after the roman god mercurius, the god of trade and science. The planet mercurius is named after the same god. Mercurius is sometimes called hydrargyrum, means ‘watery silver’. Its shine and colour are very similar to silver, but mercury is a fluid at room temperatures. The name quick silver is a translation of hydrargyrum, where the word quick describes its tendency to scatter away in all directions.
The droplets have a tendency to conglomerate to one big mass, but on being shaken they fall apart into countless little droplets again. It is used to ignite explosives, like mercury fulminate, the explosive character is one of its general themes.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
2. Cancer testis antigens and NY-BR-1 expression in
primary breast cancer: prognostic and therapeutic
implications
Dimitrios Balafoutas1
Email: dimitrios.balafoutas@uniklinik-freiburg.de
Axel zur Hausen2
Email: axel.zurhausen@mumc.nl
Sebastian Mayer1
Email: sebastian.mayer@uniklinik-freiburg.de
Marc Hirschfeld1
Email: marc.hirschfeld@uniklinik-freiburg.de
Markus Jaeger1
Email: markus.jaeger@uniklinik-freiburg.de
Dominik Denschlag1
Email: dominik.denschlag@hochtaunus-kliniken.de
Gerald Gitsch1
Email: gerald.gitsch@uniklinik-freiburg.de
Achim Jungbluth3
Email: jungblua@mskcc.org
Elmar Stickeler1*
*
Corresponding author
Email: elmar.stickeler@uniklinik-freiburg.de
1
Department of Obstetrics and Gynecology, University Hospital Freiburg,
Hugstetter Straße 55, Freiburg 79106, Germany
2
Department of Pathology, GROW- School for Oncology and Developmental
Biology, Maastricht University Medical Center, Postbus 5800, Maastricht 6202
AZ, The Netherlands
3
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-
Kettering Cancer Center, 1275 York Avenue, BOX 32, New York, NY 10021-
6007, USA
3. Abstract
Background
Cancer–testis antigens (CTA) comprise a family of proteins, which are physiologically
expressed in adult human tissues solely in testicular germ cells and occasionally placenta.
However, CTA expression has been reported in various malignancies. CTAs have been
identified by their ability to elicit autologous cellular and or serological immune responses,
and are considered potential targets for cancer immunotherapy. The breast differentiation
antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also
immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1
in breast cancer in correlation to clinico-pathological parameters in order to determine their
possible impact as prognostic factors.
Methods
The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and
NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210
randomly selected primary invasive breast cancers in order to study the diversity of different
CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were
correlated to clinico-pathological parameters and outcome data including disease-free and
overall survival.
Results
Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of
the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA
expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity
specifically was significantly correlated to shorter overall and disease-free survival (p=0.000
and 0.024, respectively).
Conclusions
Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic
marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues
as well as the frequent expression of NY-BR-1 could define new targets for specific breast
cancer therapies.
Keywords
Breast cancer, Cancer-testis antigen, NY-BR-1, Immunotherapy, Prognosis
4. Background
Breast cancer is the second most common human malignancy [1]. In recent years the progress
in systemic treatment modalities, especially endocrinological, immuno- and
chemotherapeutical strategies, have substantially reduced the proportion of women who
develop metastatic disease. In the context of these advances the importance to identify
prognostic and predictive markers is steadily increasing in order to avoid unnecessary
adjuvant therapy regimens [2].
Cancer testis antigens (CTAs) comprise an expanding family of proteins which are normally
expressed in human testicular germ cells or placental trophoblast, but not in any other normal
tissue. However, CTAs are present in various malignancies [3]. More than 100 CTA-related
genes and/or gene families have been identified, however their biological function remains
poorly understood. CTA encoding genes which are located on chromosome X are referred to
as CT-X antigens. Expression of these antigens has been found in diverse malignant human
tumors including breast cancer [4]. Because of their restricted expression, CTAs are
considered relevant to cancer biology and their prognostic relevance has been assessed in the
recent years by several studies for various malignancies [5,6]. Yet the prognostic significance
of CTAs in breast cancer still remains unclear.
Interestingly the presence of some CTAs such as, MAGE-A family members, GAGE and
NY-ESO-1 appears to correlate with clinico-pathological parameters and prognosis in
tumors, such as melanoma, non-small-cell lung cancer, multiple myeloma and other tumors
[7]. CTAs are frequently recognized by cytotoxic T-lymphocytes of cancer patients or they
can elicit a serological immune response in the autologous host [8]. Consequently, CTAs are
regarded potential candidates for the development of anti-cancer vaccines [9,10]. Specifically
NY-ESO-1 is able to elicit combined humoral and cell mediated immune response and
considered to be the most immunogenic of the above antigens. Therefore NY-ESO-1 based
vaccines have been employed in several clinical vaccination trials [11].
NY-BR-1 is a differentiation antigen of the mammary tissue, since it has been detected solely
in the epithelial cells of mammary ducts and lobules, whereas NY-BR-1 expression has not
been found in any other tissue [12]. Thus, NY-BR-1 appears to be a breast-specific protein.
At present only few reports on CTA expression patterns and their prognostic role in breast
cancer are available with limited number of patients and clinical correlations and in part
controversial findings [4,13-18]. The objective of this study was to examine the expression
pattern of the aforementioned CT-antigens as well as NY-BR-1 in breast cancer and to
correlate them with clinico-pathological parameters including patient outcome data. This
study is the first to analyze simultaneously the expression of the CTAs and NY-BR-1 in a
patient collective with long-term follow up data.
5. Methods
Patients
For this study 210 consecutive patients diagnosed with invasive breast cancer were enrolled,
according to the ethics committee of the University Hospital Freiburg, Germany (EK-
Freiburg 324/09). Standard archival paraffin blocks of primary breast cancer were retrieved
from the archives of the Department of Pathology of the University Hospital Freiburg. All
patients underwent surgery in the Breast Unit of the Department of Gynecology of the
University Hospital Freiburg. Primary treatment consisted of radical mastectomy, modified
radical mastectomy, or breast-conserving surgery including sentinel and/or axillary lymph
node dissection between the years 1991 and 2001. Patients who received neoadjuvant
chemotherapy, or who underwent preceding treatment at another institution or patients with a
second primary tumor were excluded. Median age at the time of diagnosis was 57 years.
Histopathological analyses demonstrated invasive ductal cancer in 73.8% of cases and
invasive lobular subtype in 7.6%. The remaining 18.6% were diagnosed as ductal/lobular,
mucinous (colloid), tubular, medullary and papillary carcinomas, respectively. In 88/210
(41.9%) patients lymph node involvement was histologically confirmed at the time of
surgery. 146/210 (69.5%) of the tumors were estrogen or progesterone receptor positive.
Immunohistochemical Her2/neu overexpression was recorded in 40 (21.2%) of the cases.
Follow up ranged from 1 to 107 months (mean 62, median 68 months), recurrences occurred
in 59 (28.1%) and deaths in 43 (20.5%) of women, respectively. The 63 cases with technical
failure in microarray mapping were excluded from the study.
Materials
Paraffin-embedded tissue blocks were used to generate tissue-microarrays (TMAs). At least
three representative cores of each tumor were selected. Two specimens of normal breast as
well as non neoplastic breast tissue adjacent to the lesions were used as controls. Four micron
paraffin sections were stained immunohistochemically as previously described [16]. The
following monoclonal antibodies (mAbs) were used: mAb 6C1 (Santa Cruz Biotechnology,
Inc., Santa Cruz, USA) to several members of the MAGE-A family, mAb MA454 to MAGE-
A1, mAb M3H67 also to several members of the MAGE-A family and mAb 57B to MAGE-
A4 [19-21]. Next to these, the immunoreactivity of mAb E978 to NY-ESO-1[22] and mAb
#26 (BD Biosciences Clontech, Palo Alto, USA) to GAGE was assessed. For the detection of
NY-BR-1, mAb NY-BR-1#5 previously generated by our group was utilized [23].
Evaluation of the immunohistochemical staining was performed in a blinded set up regarding
the clinical data. Scoring of the expression was performed semiquantitatively as described
previously. [24]. In brief, both percentage of stained cells and staining intensity were
evaluated. No staining or weak staining in <5% of cells was defined as 0, weak staining in at
least 5% as 1, moderate staining in up to 50% as 2 and moderate staining in >50% of cells
and strong staining of any percentage of the cells as 3. The results were subsequently
dichotomized for statistical analysis and the defined cut-off point for positivity for the
statistical analysis was set to 2.
Our data were analysed using the statistical package SPSS for windows version 17.0 (SPSS,
Chicago, Illinois, USA). The relationship among clinico-pathological parameters and CTA
6. expression were tested using the chi-square and Fisher’s exact test. Survival outcomes were
analysed with Kaplan-Meier survival functions and compared between groups with the log-
rank statistics. To determine the association of clinico-pathological parameters with survival,
univariate and multivariate Cox regression models were used. The multivariate Cox
regression model was adjusted for any known prognostic variables with p<0.05. For all tests
p<0.05 was accepted as threshold of statistical significance. Cases with missing microarrays
for some of the antigens were handled in the statistical analysis as missing data.
Results
Expression of CTAs and NY-BR1 in invasive breast cancer
Overall, CTA expression was restricted to neoplastic breast tissues and detected in 54 tumor
samples (37.2%) (Table 1). The expression was mainly restricted to the cytoplasm and only
occasionally located in the nuclei (Figure 1). A heterogeneous expression pattern was
observed regarding the percentage of positive tumor cells.
Table 1 Frequency of immunohistochemical detection of CTAs and NY-BR-1 with the
corresponding mAbs in breast cancer
n %
MAGE-A1 MA 454 21 (140) 15
mAb M3H67 17 (132) 12,9
mAb 57B 6 (133) 4,5
NY-ESO-1 E978 21 (140) 15
GAGE #26 17 (133) 12,8
MAGE-A 6C1 7 (141) 5
NY-BR-1 #5 61 (131) 46,6
n=number of cases with antigen positivity, in parenthesis total number with successful TMA
mapping for each antigen.
Figure 1 Immunohistochemical detection of cancer - testis antigens and NY-BR-1 in
primary breast cancer tissue microarrays. A: Example of moderate staining of MAGE A1
in approximately 80% of the tumor cells. The staining is restricted to the cytoplasm. B:
Strong nuclear and cytoplasmic expression of MAGE A1. C: Extensive strong nuclear and
cytoplasmic M3H67 immunoreactivity. D: Strong, mainly cytoplasmic and occasionally
nuclear 57B immunoreactivity. E: Extensive strong nuclear and cytoplasmic detection of
MAGE A (6C1). F: Focal strong, mainly cytoplasmic staining of approximately 20% of
tumor cells for GAGE. G: Strong extensive cytoplasmic and occasionally nuclear staining of
NY-ESO-1. H: Strong cytoplasmic NY-BR-1 staining of approximately 80% of cells with
scarce nuclear detection (40x objective).
MA454 reactivity (MAGE-A1) was found in 21 of cases (15%). In the 14 cases with
moderate staining (10.0%) this was restricted solely to the cytoplasm, whereas in the 7
(5.0%) cases with strong staining both the nuclei and the cytoplasm were positive.
E978 reactivity (NY-ESO-1) was also found in 21 of cases (15%). In 15 (10.7%) cases the
staining was of moderate intensity with cytoplasmic localisation and in 6 (4.3%) samples it
was strong cytoplasmatic with occasional nuclear participation.
7. M3H67 reactivity was detected in 17 (12.9%) of cases. Moderate staining was observed in 8
(6.1%) and strong staining in 9 (6.8%) of cases. On the cellular level, in the cases of
moderate staining the localisation was predominantly cytoplasmic and in the cases of strong
staining it was both cytoplasmic and nuclear.
MAb #26 reactivity (GAGE) was detected in 17 (12.8%) of cases analysed. GAGE
localisation was primarily cytoplasmic with some rare nuclear participation. Moderate
expression was found in 9 (6.8%) and strong expression in 8 (6.0%) of cases.
57B reactivity (MAGE-A4) was found in 6 (4.5%) of the arrays and the staining in these
cases was classified as strong. Localisation was cytoplasmic with concomitant nuclear
staining in approximately 20% of the nuclei in the positive areas. In 22 (10.5%) of cases we
observed a very weak unspecific diffuse cytoplasmic staining which was considered negative
in the analyses.
Seven (5.0%) cases revealed mAb 6C1 reactivity. In 3 (2.1%) of cases the staining was
moderate, predominately cytoplasmic and to a lesser extend nuclear and in 4 (2.8%) it was
strong, with both nuclear and cytoplasmic expression.
The breast differentiation antigen NY-BR-1 was immunohistochemically detected with the #5
Mab in the ductal and lobular cells of all included non neoplastic tissues as well as in 61 of
131 cases of cancer (46.6%). Its expression was predominantly cytoplasmic in the normal and
in the tumorous tissue with nuclear participation of varying degree. The staining intensity was
classified as moderate in 39 (29.8%) and as strong in 22 (16.8%) of cases. Some areas with
dot-like staining pattern in the cytoplasm were also observed. No correlation was found
between expression of CTAs and NY-BR-1.
Correlations with clinico-pathological parameters
The expression data of each CTA were grouped based on clinico-pathological characteristics
(Table 2): Age group (in comparison to median), tumor size and grade, lymph node
involvement, histological type, estrogen and progesterone receptor and HER2/neu status were
compared among positive and negative samples for each CTA. Interestingly, we observed
that CTA positivity in our cohort was restricted to grade 2 and 3 tumors and all grade 1 tumor
samples were negative for all investigated CTAs. For the other examined parameters there
was no significant difference between CTA positive and negative groups.
Table 2 Clinicopathological characteristics of breast cancer patients in our collective
n (%)
Age <median 105(50%)
>median 105(50%)
Tumor grade 1 7(3,50%)
2 92(45,80%)
3 102(50,70%)
Tumor size pT1 88(46,60%)
pT2 78(41,30%)
pT3/4 23(12,20%)
Lymph node status pN0 119(57,50%)
8. pN1/2/3 88(42,50%)
Histological type ductal 75(58,10%)
lobular 16(12,40%)
other 38(29,40%)
ER/PR status negative 58(28,40%)
positive 146(71,60%)
HER2/neu 0 54(28,60%)
1 84(44,40%)
2 11(5,80%)
3 40(21,20%)
The expression frequency of NY-BR-1 was equally distributed among the groups with
different tumor grading. Similarly we did not find any significant differences in the
expression of NY-BR-1 related with other clinicopathological parameters.
Clinical outcome analysis
Factors associated with disease-free survival (DFS) and disease specific overall survival (OS)
were analysed by Univariate Cox regression (Table 3). We observed a statistically significant
negative prognostic impact for larger tumor size (p=0.002 for both DFS and OS) and lymph
node metastases (p=0.000 for both DFS and OS). The expression of estrogen or progesterone
receptor was accompanied by longer DFS (p=0,019), but for OS this correlation did not reach
statistical significance. In the univariate Cox regression analysis NY-BR-1 did not seem to
affect recurrence or survival.
Table 3 Univariate-Cox-regression-analysis of known prognostic factors CTAs and NY-
BR-1 of breast-cancer patients
DFS OS
HR 95% CI p HR 95% CI P
Age vs median 0,884 0,530–1,475 0,637 0,987 0,542–1,796 0,966
Tumor grade 1,521 0,930–2,488 0,095 1,652 0,903–3,022 0,104
Tumor stage 1,808 1,241–2,632 0,002 1,988 1,292–3,058 0,002
Lymph node status 2,971 1,730–5,104 0 3,348 1,714–6,537 0
Histological type 0,864 0,672–1,111 0,255 0,855 0,624–1,170 0,327
ER/PR status 0,526 0,307–0,901 0,019 0,775 0,399–1,505 0,451
HER2/neu status 1,064 0,826–1,369 0,632 0,986 0,727–1,337 0,929
MAGE A1 MA454 1,278 0,564–2,898 0,557 2,284 0,910–5,732 0,078
M3H67 reactivity 2,85 1,350–6,017 0,006 4,27 1,834–9,941 0,001
57B reactivity 3,406 1,15–10,03 0,026 3,446 1,00–11,77 0,049
NY-ESO-1 E978 1,272 0,563–2,877 0,563 0,805 0,242–2,684 0,724
GAGE #26 1,988 0,875–4,516 0,101 1,98 0,739–5,303 0,174
MAGE A 6C1 1,65 0,498–5,466 0,413 1,876 0,435–8,087 0,399
NY-BR-1 #5 1,522 0,816–2,839 0,186 1,235 0,554–2,752 0,606
Abbreviations: DFS Disease free survival; OS Overall survival; HR Hazard ratio; CI
Confidence interval.
9. In contrast to NY-BR-1, Kaplan-Meier survival analysis (Figure 2) demonstrated a strong
clinical impact on survival for the immunoreactivity pattern of most of the examined CTAs.
The detected adverse effects were statistically significant for both recurrence and disease
related death for M3H67 (p-log rank=0.004 and 0.000) and 57B (p-log rank=0.015 and
0.036) immunoreactivity, respectively. MAGE-A1 positive patients had a shorter OS (p-log
rank =0.028), but no impact on DFS was observed. Additionally we found a clear, though
statistically not significant trend for negative effects of mAb #26 (GAGE) and mAb 6C1
(MAGE-A family) expression on DFS and OS: GAGE positive patients had a 19.9% shorter
DFS and a 14.7% shorter OS (p-log rank =0.090 and 0.238) and 6C1 positive patients a
23.19% shorter DFS and a 16.97% shorter OS (p-log rank =0.090 and 0.453).
Figure 2 Kaplan Meier survival analysis for disease-free (DFS) and overall-survival
(OS): In the presence (green line) or absence (blue line) of immunohistochemical
reactivity of M3H67 and 57B. p: log rank test.
Multivariate analysis identifies M3H67 reactivity as a strong prognosticator
for overall survival
In order to identify the independent prognostic factors in our cohort we performed a
multivariate Cox regression analysis (Table 4). Lymph node status was confirmed as a known
independent prognostic parameter with a hazard ratio (HR) 6.37 (95%CI 2.6–17.4, p=0.0001)
and 5.99 (95%CI 1.9–18.7, p=0.002) for DFS and OS respectively. However, M3H67
reactivity exhibited the strongest prognostic impact in this study, with a HR of 7.69 (95% CI
2.6–22.8, p=0.0001) for OS and the second strongest for DFS with a HR of 4.36 (95% CI
1.2–15.6, p=0.024). Estrogen or progesterone receptor positivity was correlated with
decreased risk of disease recurrence (HR 0.40, 95% CI 0.1–0.8, p=0.015) but was not
included in the multivariate analysis for overall survival, because it did not reach the
significance threshold in univariate analysis.
Table 4 Multivariate-Cox-regression-analysis for disease-free survival and overall-
survival of breast-cancer patients
DFS OS
HR 95% CI p HR 95% CI P
Tumor stage 0,807 0,435–1,496 0,496 1,393 0,658–2,948 0,386
Lymph node status 6,737 2,607–17,409 0,000 5,99 1,920–18,688 0,002
ER/PR status 0,405 0,196–0,837 0,015
M3H67 reactivity 4,355 1,218–15,572 0,024 7,693 2,597–22,786 0,000
57B reactivity 1,328 0,229–7,713 0,752 0,71 0,120–4,216 0,706
Abbreviations: DFS Disease free survival; OS Overall survival; HR Hazard ratio; CI
Confidence interval.
Discussion
The expression of CTAs has been described in several malignant tumors [5,6,25-27] CTAs
have been identified in melanomas, non-small cell lung and pancreatic cancer, serous ovarian
cancer, hepatocellular carcinomas, multiple myelomas as well as in breast cancer [17]. The
CTA expression frequency in breast cancer varies in the literature reaching up to 88% [14].
However, the reproducibility of the studies suffers in terms of standardization regarding
10. tumor specimen (primary tumors or metastases), methodology (RT-PCR, Western-blot or
immunohistochemistry), and the evaluation of the IHC-staining.
Using a broad spectrum of diverse mAbs, we found a total percentage for the presence of any
CTA of 37.6%, which is in accordance with most of the existing reports [14]. However, our
cohort included solely tissues from primary tumors and in contrast to other reports we valued
all cases with weak staining as negative. One study [4] found a positivity of 47% in primary
breast tumors, however, including also the tumors with 1–2% positive stained cells. The same
authors reported a significant higher percentage of CTA expression in metastatic tumors
(66%). These findings fit very well into the tumorbiological context of this gene familiy and
reflect their potential role as tumor associated antigens in tumor progression. The antibodies
tested in our study revealed the same distribution pattern, concerning isolated cells or groups
of cells, differing, however, in the degree of expression. MAGE-A1 and NY-ESO-1 were
detected at higher frequency and we recorded neither a significant coexpression nor a mutual
exclusion of the various CTAs, in accordance with the literature. However, we could not
confirm the reported higher expression of CTAs in estrogen receptor negative cases. Our
findings of a clear restriction of CTA expression to grade 2 and 3 cancers is in concordance
with other studies [28], however, the small number of grade 1 tumors did not allow us to
perform a reliable statistical analysis in this case.
CTA expression was recently associated to prognosis with an adverse impact in
gastrointestinal stromal tumors [25], oral squamous cell carcinomas [29], multiple myelomas
[30], and cervical cancers [31]. However, controversial findings were also reported
correlating CTAs with a less aggressive tumor behaviour [32,33]. Our findings demonstrate a
clear association for CTA expression and prognosis. Of all the antibodies tested in our study,
M3H67 reactivity seems to exhibit the strongest prognostic impact for the course of breast
cancer. MAGE-A proteins bind to KAP1 which is a repressor of p53 and suppress apoptosis
in MAGE-A expressing cell lines [34]. Small interfering RNA (siRNA) suppression of
MAGE genes leads to increased p53 expression and increased apoptosis in melanoma cell
lines [34], thus the overexpression of MAGE proteins in breast cancer could also protect
malignant cells from programmed cell death. For MAGE-A3, specifically, a reverse
correlation is shown in pituitary tumors between tumor supressive FGFR2 and MAGE-A3
mRNA expression[35], where siRNA down-regulation of MAGE-A3 results in p53 promoter
activation and reduced cell proliferation. GAGE proteins seem to have a similar function,
since its transfection can render cells resistant against interferon-gamma or death receptor
Fas/CD95/APO-1 induced apoptosis [36]. Clinically, overexpression of these proteins seems,
indeed, to correlate with adverse prognosis. Due to the fact, that CTAs are relatively widely
expressed, this marker could give the additional information for a substantial proportion of
breast cancer patients. 57B reactivity had a prognostic relevance in univariate analysis,
however, it could not be validated as an independent prognostic factor in the multivariate
approach. This limitation might be due to the relatively small number of cases available for
statistical analyses. 57B immunoreactivity has been previously associated with poor
prognosis in cholangiocarcinoma [37]. Additionally, M3H67 immunoreactivity, as a marker
for MAGE-A expression, mainly MAGE-A3, was found to be associated with poor prognosis
in gastrointestinal stromal tumors [38]. Moreover MAGE-A3 expression detected with RT-
PCR had an adverse prognostic effect in non-small-cell lung cancers [39]. Most previous
studies also recognized an adverse correlation of MAGE A family antigens either to the
survival or indirectly to established prognostic factors [4,40], with a unique report of MAGE-
A4 to be a favourable prognostic factor [33].
11. In the development of vaccines against breast cancer two major target antigen groups have
been proposed: CTAs because of their unique expression pattern in tumor, but not in normal
tissue and the breast differentiation antigens. Although our lack of knowledge about the
biological function of CTAs complicates their utilisation, the use of CTAs as targets for the
vaccination of breast cancer has been under debate widely the last years [41].
The exact biological function of NY-ESO-1 remains unknown. However recent experiments
indicate a possible relevance of NY-ESO-1 expression for DNA-methylation. [42]. The
frequent expression of NY-ESO-1 in our cohort could play a potential role in the application
of additional immunological therapies in breast cancer, since it has been demonstrated that
NY-ESO-1 can elicit strong CD8 and CD4 T-cell response in seropositive patients
[15,43,44]. Therefore it has been target of several vaccination efforts in the past [11]. In vivo
the T-cell responses against tumor-associated antigens seem to improve the prognosis in
hepatocellular carcinoma [45]. However, suppression of the immune response via regulatory
T-cells has also been described [46]. Several clinical trials [47] have been performed on
vaccines targeting breast cancer and two new trials are now recruiting for the use of CTAs as
targets. A recent study [16] has showed that CTA expression is more frequent in triple
negative breast cancer. This is of particular interest, since our conventional adjuvant
therapeutic possibilities in this subgroup of breast cancer are limited.
An important consideration when conducting immunohistochemical studies on the MAGE-A
family proteins is their high homology. Cross-reactivity of antibodies to MAGE-A CTAs
cannot be ruled out. At this point solely mAb MA454 to MAGE-A1 can be regarded as truly
specific for a particular MAGE-A antigen. Attempts to generate reagents to other MAGE-A
family members such as MAGE-A3, the most prevalent MAGE-A antigen on a molecular
level, have rendered mixed results. This is best exemplified by mAb 57B, which was
originally generated as a MAGE-A3 reagent [20]. Subsequent analysis indicated reactivity
with several MAGE-A family members [19]. More recent data indicate reactivity of mAb
57B to MAGE-A4 [48]. The same applies to mAb M3H67 which was originally generated to
MAGE-A3 but is now considered reactive with several members of the MAGE-A family
(unpublished data). However this does not necessarily negatively impact the prognostic value
of immunohistochemistry, but it complicates the identification of the best target for cancer
immunotherapy. Also we expected that positivity for mAb 6C1, which reacts with several
MAGE-A antigens, would be more frequent and comparable to the other anti-MAGE-A
reagents. However, in our series this was not the case. This could be based on different
affinities of the various reagents for similar antigens generating incongruent staining patters
in spite of overlapping specifity patterns.
NY-BR-1 can be identified at the protein level in physiological as well as cancerous breast
tissue [49] although recently it has been also described in a vulvar lesion [50]. The function
of NY-BR-1 in vivo has not yet been clarified. Bioinformatics analyses showing a DNA-
binding site followed by a leucine zipper motif suggest that this molecule acts as a
transcription factor. Because of five tandem ankyrin repeats NY-BR-1 could also have a role
in protein-protein interactions [49]. Our data suggest that NY-BR-1 is strongly expressed in a
great proportion of primary breast cancers (46.6%). This frequent expression of NY-BR-1 has
been previously described [12]. Humoral immune response against endogenous NY-BR-1 has
been confirmed by detecting the spontaneous NY-BR-1 directed antibody responses in breast
cancer patients, tested positive for NY-BR-1 by RT-PCR [51]. Additionally two HLA-A2
restricted peptide epitopes for NY-BR-1 that were recognized by CD8+ T cells derived from
breast cancer patients have been defined [52]. Due to the restricted expression pattern,
12. combined with the wide expression in tumors, NY-BR-1 seems to be an ideal potential target
for innovative immunotherapeutic approaches of breast cancer because of the more frequent
expression in comparison to HER2/neu, the current reference target for cancer
immunotherapy. This approach exerts even more potential since we could not confirm a
recently reported correlation between NY-BR-1 and HER2/neu expression [53].
Our analyses did not show any significant co-expression of NY-BR-1 with the CT-antigens,
neither a mutual exclusion. Since M3H67 reactivity was associated with tumor progression
while NY-BR-1 represents a differentiation antigen it might be possible that these tumors
with a high M3H67 reactivity and simultaneous absence of NY-BR-1 expression behave in a
tumorbiological aggressive fashion. In our cohort, we observed six such cases with an indeed
high mortality rate (50%), however the number of cases was too small to extract any further
conclusions.
In total 60.3% of our patients were positive for either CT-antigens or NY-BR-1 or both.
Theoretically this could facilitate polyvalent vaccines containing more than one antigen in
order to achieve in parallel targeting of a higher percentage of tumor cells in genetically
heterogeneous tumors, or vaccines that can be used without prior antigen monitoring. The
highly immunogenic potential of CT-antigens combined with immune response adjuvants
[11] is not yet fully explored but appears promising.
Conclusions
To our knowledge this study is the largest retrospective analysis of the expression and
prognostic role of numerous CT-antigens and NY-BR-1 in breast cancer. Despite the above
limitations we believe that our results underline the emerging role of the above group of
genes for prognosis and therapeutical approaches in breast cancer in the future. Especially
mAb M3H67 reactivity, probably reflecting presence of several MAGE-A antigens was
proven as a strong independent prognostic factor. The relatively small number of patients
may have concealed other important clinical correlations that appeared only as trends.
Therefore a prospective study with a much greater number of patients and the possibility of
stratification according to primary and adjuvant therapy is imperatively needed.
Competing interests
All authors declare to have no financial or non-financial competing interests. There is no
funding source to be disclosed.
Authors’ contributions
DB participated in the array analysis, performed with DD the statistical analysis and drafted
the manuscript. ES and AzH conceived the study and participated in its design and
coordination. AzH additionally performed the pathological evaluation of the specimens and
participated in the array analysis. SM was responsible for the recruitment of the patients in
the study and obtained the informed consent. MJ and SM generated the tissue microarrays.
AJ provided the monoclonal antibodies and carried out the immunochistochemical staining.
MH contributed to the evaluation of the results. GG coordinated the team and made the final
corrections. All authors read and approved the final manuscript.
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