Gentechnologie

Abstrakt

A Correlation of Pathological Characteristics and Immunohistochemistry (IHC) Based Biomarker Expression in Triple Negative Breast Carcinomas

KS Rajesh Kumar, Priyanka Maheshwari, Diganta Hazarika, Radheshyam Naik

Background: Triple-Negative Breast Cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors Estrogen Receptor (ER) or Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2). In India, several reports have suggested that TNBC incidence is higher and up to 31%. Histological features of triple-negative breast cancer are reported to be common with those of basal-like subtype, comprising of high-grade invasive ductal carcinoma, no special type, invasive ductal carcinoma with a large central a cellular zone, typical medullary carcinoma, and met aplastic carcinomas. In the present study, we aimed to correlate the pathological characteristics and evaluate IHC based expression of basal type biomarkers in triple negative breast carcinomas. Our study showed heterogeneity in histology, most of the TNBC cases in our study were IDC, NOS and there were a slightly higher percentage of atypical medullary cases as compared to other studies. Most of the cases were high grade based on modified NBR grading and majority of them turned out to be basal like on IHC. Distinctly found in our cases which had metastatic axillary lymph node was, basal immune phenotype unlike the case in other studies which demonstrated a higher proportion of lymph node negativity. As expected a high proportion of triple negative tumors showed a consistent basal cytokeratin expression (CK56-66%, CK14-72%, and CK17-68%). EGFR and p53 positivity did not show statistical significance between basal and non-basal groups. Proliferation marker Ki-67 was statistically significant in basal like groups. Gene expression profiling is the gold standard for TNBC molecular subtype classification, however, IHC is an accepted 'surrogate marker' for identifying and classifying the 'basal like group'. Our findings suggest that pathologic characteristics cannot be used to accurately classify triple-negative breast cancer into basal and non-basal groups.

Conclusion: DNA microarray based molecular profiling may not be accessible always in clinical settings, this study has emphasized that identification of basal like subtype of breast cancers can be done by doing easily available surrogate Immunohistochemical biomarkers on TNBC, and thus help to provide the patient with relevant target based therapeutic benefit.