Matrix Metalloproteinase-2 Expression as a Prognostic Marker in Breast Carcinomas

Abstract

Introduction: Matrix Metalloproteinase-2 (MMP-2) is over expressed in a variety of malignant tumours and their expression and activity are often associated with tumour aggressiveness and a poor prognosis. It serves as a prognostic marker in breast carcinoma regardless of patient age, disease stage, malignancy grade, or hormone receptor status and modulation of MMP-2 expression and activation provides a new mechanism for breast cancer treatment. Aim: To evaluate the expression of MMP-2 in breast carcinoma tumour cells and peritumoural stroma and also to analyse the findings with the existing other prognostic markers of mammary carcinoma. Materials and Methods: The present study was a retrospective study conducted on paraffin blocks of 90 cases of invasive breast carcinoma specimens received in the Department of Pathology, Sri Raamachandra Institute of Higher Education and Research a tertiary care centre in Chennai, Tamil Nadu, India, from January 2012 to June 2017. Immunohistochemical staining for MMP-2, Oestrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) was done. Statistical analysis was done on the data collected by using the software GNU-PSPP version 0.10.1. Pearson Chi-square test was used to determine significant clinicopathological differences between MMP-2 expression in positive and negative tumours. Differences were considered statistically significant when p-value was <0.05. Results: The study included 90 cases of histological proven invasive breast carcinoma. The study parameters include age, clinical staging, histopathological grade, lymphnode status, molecular subtype and MMP-2 expression in invasive breast carcinoma. Out of 90 cases, 62 cases were positive for MMP-2 and 18 cases were positive for peritumoural stroma, 30 cases were negative for MMP-2 in tumoural cells and 72 cases were negative surrounding the peritumoural stroma. Conclusion: Present study showed high MMP-2 immunohistochemical expression in breast carcinomas. There was a statistically significant association of increased MMP-2 expression with tumour stage. There was also a statistically significant association of MMP-2 in the tumour and stroma with High Grade Ductal Carcinoma In Situ (HGDCIS). There was an increased expression of MMP-2 in Luminal A subtype. Low expression was seen in the other molecular subtypes. In view of these findings and association with other studies in the literature, the present study demonstrates that the expression of MMP-2 in tumour and stromal cells could serve as a parameter of poor prognosis in breast cancer.

Keywords

• immunohistochemistry
• mammary carcinoma
• molecular subtyping