Prognostic Influence of Tumor Stroma on Breast Cancer Subtypes.

INTRODUCTION: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 matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) on prognosis in different breast cancer subtypes. MATERIALS AND METHODS:A total of 247 tumors of patients with primary ductal invasive breast cancer were categorized into 1 of 4 major subtypes, using the 3 standard immunohistochemical markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor/Neu 2 [HER2] receptor status). An immunohistochemical study was performed using tissue arrays and specific antibodies against MMP-9, MMP-11, and MMP-14, and TIMP-1 and TIMP-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, MMP-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: 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.