Prognostic Influence of Tumor Stroma on Breast Cancer Subtypes

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.

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.

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.

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.