Breast carcinoma is a leading cause of cancer death in women. It is the most common malignant neoplasm, with more than 1,000,000 cases occurring worldwide annually Breast cancer may present as occult primary or as a metastatic lesion.
Metastatic adenocarcinomas of unknown origin makes around 3% of all the cancer patients It is among the 10 most common malignancies. The prognosis and therapy of the patients with metastatic adenocarcinomas are linked to the site of origin.
Origin of metastatic adenocarcinoma by morphology alone is difficult. The primary may be from any of the many possible sites, including breast, lung, gastrointestinal tract, endometrium and ovaries. Studies have shown that Gross cystic disease fluid protein 15 (GCDFP-15) is a specific and sensitive marker for breast cancer.
First identified in the fluid of breast cysts and in the serum of patients with mammary carcinomas. The major constituents in breast cyst fluid being GCDFP-15, GCDFP-24 and GCDFP-44. Encoded on chromosome 7.
It also inhibits apoptosis by T-cells. It the most reproducibly present in breast carcinomas This protein is induced by prolactin and androgen.
Non-neoplastic serous salivary gland acini, bronchial serous glands, seminal vesicles and apocrine skin adnexa are immunoreactive. Renal tubules, ovarian surface epithelium and urothelium are negative Staining is cytoplasmic, often with paranuclear enhancement in mammary carcinomas.
To assess the immunohistochemical expression of GCDFP-15 in Primary Breast Tumors To compare this expression with expression of GCDFP-15 in known Metastatic breast adenocarcinoma Carcinomas. To assess the utility of GCDFP-15 as a diagnostic marker for metastatic breast cancer
SETTING: Pathology Department of Shaukat Khanum Cancer Hospital LahoreINCLUSION CRITERIA:Mastectomy specimens from female patients with primary tumor and corresponding lymph node metastases were included in the study.Control were known cases of adenocarcinoma lung, kidney, colon, endometrium and ovraies.EXCLUSION CRITERIA:The specimens with poorly preserved tumors were excluded.
50 Mastectomy cases were included -Tissue from primary tumor -Tissue from involved lymph nodes. 50 controls were included from known adenocarcinomas - Lung, ovary, colon endometrium and kidney.
Representative sections were taken, processed and stained with hematoxylin and eosin to see the tumor morphology.
The immunohistochemical stain GCDFP-15 wasperformed simultaneously in the same batch,according to the specifications given by themanufacturer, on sections made from - Primary breast carcinomas. - Metastatic breast adenocarcinoma in regional axillary lymph nodes from respective mastectomy specimens. - Study Controls
Expression of biomarker (GCDFP-15) in primary tumors was compared - With the expression of this biomarker in metastatic carcinoma. - On the study controls.
Intensity of cytoplasmic staining Negative Weak Moderate Strong% of cytoplasmic staining Negative: No tumor cell Focal positive: Less than 10% Diffusely positive: More than 10%
Distribution of Cases Accordingto Age Age of the patients No. of patients (Years) (%) 20-29 3(6%) 30-39 9(18%) 40-49 16(32%) 50-59 12(24%) 60-69 7(14%) 70-79 3(6%) Mean 47.76years +_SD 13.05 Median 48years Range 21- 76years
Distribution of cases according to pathologic characteristics Pathological characteristics Findings Total no of patients 50 Tumor Size Range 1.0cm to 12.cm Mean 4.44cm +- SD 2.48 Tumor Type Invasive ductal carcinoma (NOS) 47(94%) Invasive lobular carcinoma 3(6%) Lymph node status No of lymph nodes isolated in each case Range 2.0 to 24 Mean 12.62 +_ SD 4.94 No of involved lymph nodes Range 1.0 to 24 Mean 6.14 +- SD 4.40 Size of metastatic deposit Range 0.4cm to 2.2cm Mean 1.2cm +_ SD 0.49
GCDFP-15 positivity was observed in - 92% of the primary tumors. - 88% of metastatic breast carcinomas (p= 0.000). The concordance value of GCDFP-15 expression between the primary and metastatic tumors was found to be significant i.e. 96%.
No statistically significant difference of GCDFP- 15 expression was seen between primary and their respective metastatic tumors (p=0.251). All 50 study control cases of adeno- carcinomas were negative for GCDFP-15.
Sensitivity, specificity and positivepredictive values were calculated byapplying table of 2x2 taking histopathologyas gold standard.
These values found in primary tumors were 92% (sn), 84% (sp) and 77.7% (pp) respectively. In metastatic tumors, these values were 88% (sn), 84% (sp) and 87.7%(pp)respectively. The sensitivity, specificity and predictive values are comparable in both primary and metastatic tumors.
Gross cystic disease fluid protein (GCDFP-15) is a sensitive and a specific marker for detection of primary and as well as metastatic breast adenocarcinomas. It shows significant concordance between primary and metastatic breast carcinoma to the corresponding lymph nodes. It can be used to identify breast primary in metastatic tumors of unknown origin.