Prognostic Significance of Tissue Inhibitor of Metalloproteinase-1 in Breast Cancer

Abstract

Introduction. Despite advances in breast cancer systemic treatment, new prognostic and predictive factors are still needed. Tissue inhibitor of metalloproteinase-1 (TIMP-1), a physiologic inhibitor of matrix metalloproteinases (MMPs), can act in both pro- and antitumoral effects. As role of TIMP-1 in breast cancer is controversial, we aimed to determine the prognostic significance of TIMP-1 in breast cancer. Methods. A single center-based case-control study was applied. Primary breast cancers from women with early stage disease treated with standard adjuvant therapy were analyzed by gene expression microarrays and immunohistochemistry for TIMP-1. Results. At the optimized cut-point, patients with high TIMP-1 RNA levels had a significantly shorter time to relapse, with a hazard ratio (HR) of 1.64 (P=0.04), but without significant differences in overall survival (HR 1.29, P=0.37). Although cytoplasmic overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.0, P=0.92), there was a tendency for short overall survival in patients with high expression (HR 1.41, P=0.21). Conclusions. Our data indicate that elevated TIMP-1 RNA levels are independently prognostic for early recurrence, and there is a tendency for association of high cytoplasmic TIMP-1 protein levels with short survival in primary breast cancer.