Study of Her2/Neu Expression in Breast Carcinoma and Correlation with Various Prognostic Parameters

Background: Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. High levels of human epidermal growth receptor 2(HER2/NEU) expressions are associated with recurrence and death in breast cancer (BC). Though it is associated with poorer survival but its main importance is as predictors of response to agents that target this transmembrane protein (transtuzumab). The aim of the study was to evaluate the expression pattern of HER2/NEU in invasive component of breast carcinoma and correlate with various prognostic parameters such a tumour size, histologic grade, histologic type, regional lymph node status, and proliferative marker Ki67. Study Setting & Design: A total of 112 breast cancer cases were studied for the histomorphological features followed by immunohistochemical study in the Department of Pathology of a tertiary care hospital. Material and methods: The lumpectomy or mastectomy specimens were fixed on 10% neutral buffered formalin immediately after surgery in 10 fold volume. Important clinical information from patients were collected in Performa. Finally routine hematoxylin and eosin sections were examined to confirm presence of invasive cancer, ascertain histological types, Histological Bloom Richardson grade (BRG)1 and axillary lymph node status. IHC of HER2/NEU protein was done using HER2/NEU antibody following standard procedures. The tumour was also immunostained with Anti ER, Anti PR, and Ki67 primary antibody. Statistical Analysis: Data was analyzed by SPSS software. Results and observation: The mean age of breast cancer presentation in this study was 44.6 years with standard deviation 11.24.This IHC evaluation for HER2/NEU was positive with 3+ score in 18.75% of cases. The data of HER2/NEU expression profiles were correlated with 3 BRG histologic grades of the tumours, it showed a positive association with high histologic grade. HER2/NEU profiles were inversely correlated with ER, PR expression (p value < 0.05). The HER2/NEU expression profiles was also correlated with tumour size and a significant relationship was found (p = 0.041).HER2/NEU positive tumours were belonged to mostly IDC.HER2/NEU expression profile was correlated with proliferative index Ki67 expression in this study and found a direct relationship (p < 0.005). Lymph node status and HER2/NEU showed a significant statistical correlation (p = 0.037). Discussion: The over-expression of HER2/NEU is associated with poorer prognosis, high grade features and resistant to usual chemotherapy10. Our study also revealed that the Patients with higher levels of HER2/NEU- overexpression or amplification had statistically significant with lower levels of ER and PR positive tumours. We also found that when Her 2 neu was positive in tumours along with ER and PR, then it was mostly high BRG and High Ki67.The new addition from our study wasHER2/NEU expression profile correlation with Proliferative marker Ki67 which revealed a positive association. Conclusion: The expression pattern of HER2/NEU protein showed a strong correlation with high Ki67 expression which means these tumours are likely to have higher proliferative fractions leading to high probability of recurrence without management by herceptin therapy.