Prognostic Influence of Tumor Stroma on Breast Cancer Subtypes

Abstract

Aims: The objective of the present work was to evaluate the impact of the phenotype of both intratumoral mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs), assessed as to their expression of MMPs and TIMPs on prognosis in different breast cancer subtypes. Materials and Methods: 247 tumors of patients with primary ductal invasive breast cancer were categorized into one of four major subtypes, using the three standard immunohistochemical markers (ER, PR and HER/Neu 2 receptor status). An immunohistochemical study was performed using tissue arrays and specific antibodies against matrix metalloproteinase (MMP)-9, -11 and -14, and tissue inhibitors of metalloproteinase (TIMP)-1 and –2. Results: MMP-11 expression by MICs was significantly and strongly associated with prognosis in all breast cancer subtypes. There were other significant associations with poor prognosis in Luminal A tumors: expressions of MMP-9, -11, and TIMP-2 by CAFs, in Luminal B tumors: MMP-14 expression by MICs and TIMP-2 expression by MICs, in HER-2-positive tumors: expression of MMP-9 by MICs and in triple-negative breast cancers (TNBC): expression of TIMP-1 by MICs. Conclusion: Characterization of both tumor stromal CAFs and MICs, with regard to the expression of MMPs and TIMPs, improve the prognostic evaluation of all breast cancer subtypes.