Estrogen Receptor, Progesterone Receptor Profile in Association with CK 5/6 Immunohistochemical Status in Proliferative, Preinvasive and Malignant Epithelial Neoplasms of Breast

Abstract

Introduction: Breast carcinomas have shown increasing incidence across the world over the recent few years. The different epithelial cells play a role in the pathogenesis of different breast lesions consistent with the varying cytokeratin (CK) expression profiles. The luminal cells express CK 8 and 18 while myoepithelial cells show CK 5/6 and CK 17 expression. Triple Negative Breast Cancers (TNBC) (hormonal receptors and Human Epidermal growth factor Receptor 2 (HER2)/neu negative) express basal cytokeratins and histopathologically show metaplastic to medullary features while luminal breast cancers with glandular differentiation show hormonal receptor or HER2 expression. Also basal cells are characteristic of benign lesions like epithelial hyperplasia, fibroadenoma etc. while being absent in atypical hyperplasia and preinvasive lesions. Aim: To study cytokeratin 5/6 and Estrogen Receptor/Progesterone Receptor (ER/PR) expression pattern in proliferative, preinvasive and malignant lesions of breast. Materials and Methods: An observational cross-sectional study was undertaken in the Department of Pathology in a tertiary care hospital in East India, from January 2019 to June 2020. A total of 41 samples diagnosed as proliferative (Usual Ductal Hyperplasia (UDH)/Atypical Ductal Hyperplasia (ADH), preinvasive Ductal carcinoma in Situ (DCIS) and invasive breast carcinomas were selected by systematic random sampling. Immunohistochemical examination was done using monoclonal antibodies against Cytokeratin 5/6 and ER/PR/HER2 after obtaining thin sections from formalin fixed paraffin embedded blocks and retrieval of antigen. The data was interpreted by light microscopy using a semi-quantitative method with respect to prefixed parameters and statistical analysis was done by Chi-square test and Fischers-exact test using Statistical Package for the Social Science (SPSS) version 25.0. Results: Of the 41 cases, three were of proliferative lesions (UDH+ADH), 1 (33%) (UDH) showed positive CK 5/6 expression and 2 (66.7%) (ADH) showed negative CK 5/6 expression. Of two preinvasive lesions (DCIS), 100% of them showed negative CK 5/6 expression. On categorisation of carcinoma cases into molecular subgroups as indicated by surrogate immunohistochemical expression, it was found that majority of the cases (20) exhibited Luminal-A Like molecular profile constituting 55.6% of total. This was followed by an equal incidence of HER2/neu enriched (non luminal) and triple negative phenotypes. Both Luminal B-like (HER2-positive) and Luminal B-like (HER2-negative) were three in number contributing to 8.3% of total each. Out of 36 malignant cases, 5 (13.9%) showed positive CK 5/6 expression while 31 (86.1%) showed negative CK 5/6 expression. All these five cases showing positive CK 5/6 expression belonged to triple negative molecular subtype and this association between the molecular subtypes and CK 5/6 expression pattern was statistically significant p-value=0.0034. Of total five TNBC cases, 2 (40%) were reported to have weak positive CK 5/6 immunostaining, while 3 (60%) of the cases had moderate intensity. Still none of these cases exhibited strong immunostaining. The single UDH case reported in present study, exhibited strong positive immunostaining with CK 5/6. Conclusion: The proliferative lesions consisting of both luminal and myoepithelial cells like UDH showed strong membranous and cytoplasmic expression while ADH, DCIS, and invasive breast carcinoma comprising primarily of luminal epithelial cells were negative for basal cytokeratin 5/6 expression. These group of breast carcinomas belonged to other immunophenotype categories apart from TNBC. However, a special immunophenotype TNBC group, negative for ER/PR and HER2/neu was strikingly positive for CK 5/6 and a statistically significant association was found.

Keywords

• cytokeratins
• invasive ductal carcinoma
• not otherwise specified
• triple negative breast cancers