Cytoplasmic Her-2/neu Internal Domain Expression a Truncated form Confirmed by Double Staining Immunohistochemistry Identifies an Aggressive Breast Cancer Phenotype
Journal Title: GUJARAT CANCER SOCIETY RESEARCH JOURNAL - Year 2014, Vol 16, Issue 1
Abstract
Her-2/neu over expression is found in women with breast cancers and recent studies indicated prognostic significance of Her-2/neu over expression may be due to associated expression of p95Her-2/neu, a truncated form of Her-2/neu lacking the extracellular domain. The aim of the study was to detect truncated form of Her-2/neu (p95Her-2/neu) by double staining immunohistochemistry method on formalin fixed paraffin embedded tumor tissues of breast cancer patients and compare its expression with clinicopathologic parameters and disease outcome. In this study, 90 patients with breast cancer were enrolled. Double staining immunohistochemistry method was performed to confirm cytoplasmic staining as truncated form of Her-2/neu, using antibodies against Her-2/neu internal domain (CB11), Cytokeratin (polyclonal, and AE1/AE3) and Her-2/neu external domain (SP3) in three combinations. Over expression of membranous Her-2/neu internal domain, cytoplasmic Her-2/neu internal domain and Her-2/neu external domain was found in 70%, 30% and 33% of patients with breast cancer, respectively. A significant positive correlation of membranous Her-2/neu internal domain expression was observed with cytoplasmic Her-2/neu internal domain expression (p=0.001) and Her-2/neu external domain expression (p=0.001). Further, univariate survival analysis indicated that patients with cytoplasmic Her-2/neu internal domain positivity significantly associated with reduced disease free survival (DFS) and overall survival (OS) as compared to cytoplasmic Her-2/neu internal domain negativity. Multivariate survival analysis also indicated patients with cytoplasmic Her- 2/neu internal domain positivity significantly associated with reduced DFS as compared to respective counterpart. Cytoplasmic Her-2/neu (truncated Her-2/neu) identifies an aggressive phenotype of breast cancer. Double staining immunohistochemistry technique may provide a unique tool for evaluation of truncated Her-2/neu in breast cancer.
Authors and Affiliations
Kruti Rajvik, Manoj Shah, Hemangini Vora
Keywords
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