This document discusses biomarkers and recent grading systems for prostate carcinoma. It begins by introducing prostate cancer as the second most commonly diagnosed malignancy in men. It then discusses several biomarkers used for diagnosis and prognosis, including prostate-specific antigen (PSA) and related factors like PSA density and kinetics. Newer biomarkers discussed include PCA3, TMPRSS2-ERG gene fusion, and circulating tumor cells. The document also covers recent grading systems like the Gleason score and 2014 ISUP grade groups which stratify prognosis.
Audio and slides for this presentation are also available on YouTube: http://youtu.be/ukXhuy5cXrE
Huma Q. Rana, MD, a cancer geneticist with Dana-Farber Cancer Institute, explains the cancer risk associated with BRCA1 and BRCA2 gene mutations. This presentation was originally given on July 23, 2013 as part of the "What Every Woman Should Know" event put on by Dana-Farber's Susan F. Smith Center for Women's Cancers.
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
BRCA – Importance in Hereditary Breast & Ovarian CancerLifecare Centre
BRCA – Importance in Hereditary
Breast & Ovarian Cancer
DGF & WOW India
presentation was made by
Dr Sharda Jain
based on presentation made by
Dr Sunil Tadepalli
Audio and slides for this presentation are also available on YouTube: http://youtu.be/ukXhuy5cXrE
Huma Q. Rana, MD, a cancer geneticist with Dana-Farber Cancer Institute, explains the cancer risk associated with BRCA1 and BRCA2 gene mutations. This presentation was originally given on July 23, 2013 as part of the "What Every Woman Should Know" event put on by Dana-Farber's Susan F. Smith Center for Women's Cancers.
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
BRCA – Importance in Hereditary Breast & Ovarian CancerLifecare Centre
BRCA – Importance in Hereditary
Breast & Ovarian Cancer
DGF & WOW India
presentation was made by
Dr Sharda Jain
based on presentation made by
Dr Sunil Tadepalli
EAU - Guidelines on Prostate Cancer dr. ali mujtabaDr Ali MUJTABA
EAU - Guidelines on Prostate Cancer Organ Confined by Dr. Ali Mujtaba, Sindh Institute of Urology and Transplantation (SIUT)
https://www.youtube.com/watch?v=kXX9ItF4as4
https://www.youtube.com/watch?v=0m4YUI6Rr5w
Role of Prostate Health Index in the changing landscape of prostate cancer di...Lincoln Tan
The prostate health index is superior to PSA and %fPSA, and can be integrated with MRI in predicting who needs prostate biopsies, and sparing men from unnecessary biopsies.
Hematopoietic Stem Cell Harvesting and Mobilization.pptxroysudip900
procedure of bone marrow stem cell harvesting for bone marrow transplant by apheresis. mobilization of stem cell from bone marrow to peripheral blood. GCSF mobilization. Apheresis principle and procedure. stem cell from bone marrow collection. effect of stem cell collection form different sources. newer drugs for stem cell harvesting. adequate dose of stem cell to be collected. minimal invasive procedure.
Recent advancement in prevention and management of GVHD.pptxroysudip900
advances in prevention of GVHD by different investigational and approved methods of graft modulating, drugs, chemotherapy, analysis of published data, improved survival, future direction. different sources of stem cell and strategies to prevent mortality and morbidity
diffuse large B cell lymphoma recent molecular classification
molecular classification and their time frame with references
Recent advantages of DLBCL and thier implication in therapy
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
4. Introduction:-
• Prostate cancer is the 2nd most common
diagnosed malignancy (Incidence)
• 5th leading cause of cancer-related death
• Most prevalent cancer of men
• Newer biomarkers needed for early detection
and therapeutic targets for needed
5. Prostate-specific antigen (PSA)
• PSA is present in small quantities in the serum of
men with healthy prostates
• PSA is the most used test to detect carcinoma.
• limited specificity and an elevated rate of over
diagnosis
6. PSA elevated in
prostate cancer,
prostatitis,
irritation,
benign prostatic hyperplasia (BPH),
recent ejaculation and
Digital rectal examination(DRE)
7. PSA in Serum
Disruption of this epithelium due to disease
diffusion of the antigen
into blood
causes of elevated blood levels of PSA
o Obesity reduce serum PSA levels
8. Screening
• annual screening in men of age 50 and older
• Normally less than 4 ng/mL
• PSA levels between 4 and 10 ng/mL are suspicious
for malignancy
• >10ng/mL considered as high risk for malignancy
10. Histology
• PSA is produced in the epithelial cells of the
prostate
• can be demonstrated in biopsy samples by using
IHC
• PSA remains present in malignant prostate cells
• Prostate cancer cells generally have variable or
weak staining for PSA due to the disruption of their
normal functioning
11. • individual prostate cancer cells produce less PSA
than healthy cells.
• increased number of cells
causes raised serum levels
• identify metastasis.
• some high-grade prostate
cancers may be entirely negative for PSA
Normal prostate tissue with PSA IHC
12. PSA kinetics:-
• PSA velocity
–rate of increase of PSA per year (ng/ml/year)
–valuable in prostate cancer prognosis.
–increased by more than 2.0 ng per milliliter
during the year -higher risk of metastasis
• PSA doubling time (PSA DT)
–identify life threatening disease before start of
treatment (n=>10 yrs)
13. Free PSA
• not protein bound - 'free PSA'.
• In prostate cancer the ratio of free (unbound) PSA
to total PSA is decreased.
• The risk of cancer increases if the free to total ratio
is less than 25%
• Help to eliminate unnecessary biopsies when PSA
levels between 4 and 10 ng/mL.
14. Inactive PSA
• Proteolytically active PSA has been shown to have
an anti-angiogenic effect
• inactive subforms are associated with prostate
cancer
• identified by MAb 5-D3-D11
• inactive proenzyme forms of PSA is another
potential indicator of disease.
15. PSA Density (PSA-D)
• PSA density =
total PSA (ng/ml)
prostate volume (ml)
• In benign diseases less than 0.06 ng/ml2
• Increased value associated with the risk prostatic
carcinoma
• Omitting prostate biopsy with Gleason Score ≥7
tumors with PSA-density
–≤0.07 ng/ml2 may miss 6.9%
–0.10 ng/ml2 may miss1.3%
16. • PSA-density
–Information about biopsy decisions,
–spare some men from unnecessary prostate
biopsy and
–diagnosis of low-grade prostate cancer.
BUT
• its use for biopsy decisions is conflicting
• not commonly recommended in guidelines
*Nordström, T., Akre, O., Aly, M., Grönberg, H., & Eklund, M. (2017, December 19).
Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer.
https://www.nature.com/articles/s41391-017-0024-7
17. Post-treatment monitoring
• PSA levels are monitored periodically (every 6–36
months) after treatment of high-risk disease
• less frequently in patients with lower-risk disease
• After successful therapy PSA becomes undetectable
within a few weeks.
• A subsequent rise above 0.2 ng/mL - recurrence
18. • After successful radiation therapy little PSA may be
detected
• recurrent prostate cancer - "biochemical
recurrence"
21. aggressiveness determination by
PHI and
the four kallikrein panel
assessment of cancer prognosis
Prolaris®
Oncotype DX®
Prostate-Specific Membrane Antigen (PSMA)
select the treatment by
androgen receptor splice variant-7 (AR-V7)
22. PCA3
• only expressed in human prostate tissue
• the gene is highly overexpressed in prostate cancer
• because of its restricted expression profile, the
PCA3 RNA is useful as a tumor marker
• PCA3 is also known to as DD3
23. Discovery:-
• PCA3 was discovered in 1999 by MJ Bussemakers et.
al.
• done by comparing the mRNA expression patterns
of normal v/s tumor tissue of the human prostate
• then cDNA library of mRNA extracted
24. • six overlapping genomic phages that cover
the DD3 gene were isolated and characterized
• then structure of the DD3 transcription unit
identified
Genetic structure of PCA3 gene
25. Genetic structure:-
• DD3/PCA3 gene present in ch 9q21–22
• three reading frames
• DD3 cDNA has the high density of stop codons
• lack of an extensive open reading frame.
• the DD3gene consists of four exons
26. • alternative polyadenylation occurs at three different
positions in exon 4 (4a, 4b, and 4c)
• exon 2 is only present in 5% of the cDNA clones
• often skipped by alternative splicing
Structure of the DD3 transcription unit
27. • the DD3 gene is about 25 kb
• the first exon is relatively large (appr. 20 kb);
• whereas exon 2,3 and 4 are small
• several small open reading frames scattered
throughout the DD3 gene
• located in exons 3 and 4a
• So, the protein product is likely to be very small.
28. Relation of PCA3 with Prostate cancer:-
• 10–100 fold overexpression in the tumor areas than
adjacent non-neoplastic prostate tissue
• Expression is observed in almost all stages of the
tumors
• Up-regulation of DD3 expression is an early event in
prostate cancer development
29. • PCA3 expression is found in well-differentiated,
moderately differentiated and poorly differentiated
tumors
• Trend toward more expression in the poorly
differentiated tumors
30. Use as biomarker
• Urine-based PCA3 diagnostic tests is noninvasive
• Compared to serum PSA, urinary PCA3 has
–lower sensitivity but
–higher specificity and
–better positive and negative predictive value.
• PCA3 is independent of prostate volume compared
with PSA
31. • Suspected by DRE and PSA, approximately 60% of
cases 1st biopsy is normal
• On repeat testing, 20-40% have an abnormal biopsy
result
• PCA3 is useful to avoid these repeated biopsy
• Also found in metastatic lesions
32. PCA3 and prognosis:-
• PCA3 score and grading correlated statically with
prognosis
• PCA3 score lower than 51 and Gs ≤ 6 shows
comparatively good prognosis
• PCA3 score higher than 51 and a Gs ≥ 7 – poor
prognosis
33. Commercial availability:-
• A commercial kit called the Progensa PCA3 test is
marketed by Gen-Probe
• the first portion of urine
after prostate message
• The PCA3 Test measures
both PCA3 and PSA mRNA in a urine sample
• The PSA mRNA measurement ensures that prostate
cells were collected in the sample
34. • Using RT-PCR , PCA3 and PSA mRNA are amplified
from the sample
• The result is reported as a ratio of PCA3 mRNA to
PSA mRNA
• samples having cancer -higher PCA3/PSA ratios
• PSA mRNA measurements below a certain
detection amount produce an inconclusive test
35. • PCA3 levels were significantly higher among men
who were subsequently diagnosed
• the PCA3 score was significantly higher with
Gleason ≥7 tumors , clinical stage T2 disease
36. PSA glycoforms
• Based on different glycosylation patterns between
PCA patients and healthy subjects
• Significant increase of α2,3-sialic acid in malignancy
than BPH
• Identifies aggressive PCA and correlates with
Gleason score
37. • The cutoff value is 30%
• Helps in differentiates between high-risk PCa and
the groups of BPH, low- and intermediate-risk PCa
• PSA fucosylation also increases
• Decrease in core fucosylation of PSA in carcinoma
38. TMPRSS2:ERG fusion gene
• Transmembrane Protease; Serine 2
• Common in hematologic malignancies
• Can be detected in urine samples obtained after a
prostate massage
• RT-qPCR
• TMPRSS2:ERG score =
TMPRSS2:ERG mRNA
PSA mRNA
39. • TMPRSS2:ERG score and PCA3 score combined
significantly increased the predictive value of
diagnosis
• TMPRSS2:ERG score associated with –
the biopsy Gleason score and
tumor clinical stage.
• ExoDx Prostate IntelliScore measures
PCA3, SPDEF, and ERG
40. MicroRNAs
• miRNAs are involved in all steps of carcinoma
development,
cell proliferation,
differentiation, and
progression.
• cancer stem cells proliferation and differentiation
miR-34 family and
let-7 family upregulated
• apoptosis
miR-21 is upregulated to reduce apoptosis
41. Circulating tumor cells
• Tumor cells can acquire the ability to pass vessel
walls and enter into the bloodstream.
• Facilitate the establishment of metastatic focus
• High proportions are commonly found in advanced
metastatic stages,
• Very rare in early stages
42. • CTCs present a heterogeneous phenotype, due to-
intratumor heterogeneity and
differences between primary tumor and
metastases
• Heterogeneity linked with therapy resistance
• Help to make therapeutic decisions
• No sufficient prognostic value in localized ca.
43. • CellSearch® platform has approved for monitoring
of metastatic breast, colon, and Prostate cancer
• Based on immunomagnetic capture followed by a
combination of positive and negative
immunological selections.
• In advanced stages, Androgen Deprivation Therapy
(ADT) help to slow carcinoma progression by CTC
identification
44. Androgen receptor(AR)
• SPOP or FOXA1 mutations
• Transcription factors are the main driver of CRPC
development
• AR gene amplification and overexpression,
• AR mutations, and
• expression of constitutively active AR variants
(AR-Vs).
• OncotypeDX AR-V7 Nucleus Detect
45. Prostate Health Index (PHI)
• PHI combines total PSA, fPSA, and p2PSA
•
• Useful in men >50 years, PSA between 4 and 10
μg/L, and a nonsuspicious digital rectal examination
(DRE).
• PHI demonstrated a higher accuracy than total PSA
and %fPSA
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𝐟𝐏𝐒𝐀
𝐱 𝐭𝐨𝐭𝐚𝐥𝐏𝐒𝐀
46. • Significantly higher in patients with a Gleason score
≥7 than score 6.
• Values for PHI high in patients with clinical stage
T2–T3 than stage T1c.
• PHI density has a higher discriminative ability to
detect clinically significant PCa than PHI
47. Four-kallikrein panel
• Comprises
• total PSA,
• fPSA,
• iPSA, and
• human kallikrein 2
• Excellent diagnostic tool for high-grade carcinoma
48. • To reduce the over detection
• 30% of biopsies could be avoided
• able to predict the long term development of
distant metastasis
49. Prognostic factors
• Gleason score - most valuable and conventional
predictor
• Gleason score ≥7 require a radical treatment
• Gleason score 6 could probably have carcinoma
with low risk of progression
• Active surveillance is the best option for them.
50. Prolaris test
Oncotype DX test
• Recommends for very-low and low risk PCa in
patients
• Choice between active surveillance and definitive
therapy.
• Prolaris evaluate of 31 cell cycle progression genes
related to cancer proliferation
• Oncotype DX test evaluate 5 housekeeping genes
related to metastasis.
51. Prostate-Specific Membrane Antigen
• Transmembrane protein
• Expressed in all types of prostatic tissue
• Acts as a glutamate-preferring carboxypeptidase
• Upregulated in androgen deprivation
• Independent indicator of poor prognosis
• Possible target for chemotherapy
52. Recent Biomarkers
• Prostate Stem Cell Antigen - difficult
• AMACR (Alpha Methyl Acyl Coenzyme A Racemase)
• TFF3
–high expression in prostate cancers but
statistically insignificant predictors by using urine
samples
• GOLPH2 (Golgi phosphoprotein 2) – in study
53. Limitations
• Performance has not been established in patient
had biopsy less than three months ago
• Effect of medications unknown
• Other diagnostic procedures as radiation may affect
56. Gleason grading system
• Original scheme established in the 1960–70s
• Incorporated into the WHO classification of prostate
cancer
• New “grade group” system proposed by the 2014
ISUP consensus
• Adopted by the who classification of tumours of the
prostate in 2016
57. The classical Gleason system
• Five histological growth patterns (grades) based on
architectural patterns
• Gleason 1 represents the best differentiated
most favorable prognosis,
• Gleason 5 the least differentiated
poor prognosis.
58. • Gleason pattern 1 - well-circumscribed, nodular
lesion- VERY RARE
• Gleason pattern 2 –
–variations in sizes of the neoplastic glands,
–slightly increased stroma between the glands,
and
–slight irregularity at the periphery of the nodule
–rare
59. • Gleason pattern 3 –
–most common pattern,
–distinct neoplastic glands,
–typically small, but often of variable sizes and
–infiltrating into the stroma in between the benign
glands.
• Gleason pattern 4 –
• fused glands, no individual or distinct gland,
• broad, irregular cribriform patterns
60. • Gleason pattern 5 –
–Comedo type necrosis
• Gleason score = the sum of the primary and
secondary patterns (grades)
• With just one pattern, the primary and secondary
patterns are considered the same
61. • The major changes in the 2016 WHO blue book are
–Cribriform glands should be assigned Gleason
pattern 4.
–Glomeruloid glands should be assigned Gleason
pattern 4.
–Mucinous carcinoma should be assigned Gleason
pattern 4.
• According to the 2004 WHO blue book, rare
cribriform glands diagnosed as pattern 3
62. Grade groups:
• By 2014 ISUP consensus conference on Gleason
grading of prostatic carcinoma
• These grade groups are as follows:
–Grade group 1: Gleason score ≤6
–Grade group 2: Gleason score 3 + 4 = 7
–Grade group 3: Gleason score 4 + 3 = 7
–Grade group 4: Gleason score 4 + 4 = 8, 3 + 5 = 8,
5 + 3 = 8
–Grade group 5: Gleason scores 9–10
63.
64. Take home message
• Prostate cancer is the 2nd most common diagnosed
malignancy (Incidence); Most prevalent cancer of
men
• PSA remains the most used marker to detect
carcinoma
• Most important limitation is over diagnosis
• D'Amico Criteria Risk categorization is done by
combination of PSA, Gleason score, clinical stage
65. • PSA velocity >2.0 ng /ml -higher risk of metastasis
• The risk of having cancer increases if the free to
total PSA ratio is less than 25%
• Post-treatment PSA becomes undetectable within a
few weeks
• PCA3 is highly overexpressed in prostate cancer
(10–100-fold)
• Urine-based PCA3 estimation by RT-qPCR
66. • TMPRSS2:ERG fusion gene estimated from urine by
RT-qPCR
• Therapy resistance can determined by CTC
• Prostate-Specific Membrane Antigen is a marker of
prognosis
• Gleason grading system based on architectural
patterns
• WHO Grading 2016 based on modified Gleason
grading, the grade groups