Abstract P5-04-07: Epithelial-mesenchymal transition phenotype in breast cancers is associated with clinicopathologic factors indicating aggressive biologic behavior and poor clinical outcome

Abstract

Abstract Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. EMT in epithelial tumors is a reversible process and expected to be involved in invasion, metastasis and chemoresistance of cancer cells. EMT-inducing factors down-regulate E-cadherin and up-regulate extracellular matrix proteins such as fibronectin. Cancer tissue may display a wide spectrum of expression phenotypes of EMT-related proteins. However, little is known about the clinical significance of the different EMT phenotypes in breast cancers. We investigated expression pattern of EMT-related proteins, E-cadherin and fibronectin in 1,498 invasive breast carcinomas by using immunohistochemistry on tissue microarrays. EMT phenotypes were divided into complete type (E-cadherin-negative and fibronectin-positive); incomplete type, including hybrid (E-cadherin-positive and fibronectin-positive) and null (E-cadherin-negative and fibronectin-negative) types; and a wild type (E-cadherin-positive and fibronectin-negative). We correlated EMT phenotype with clinicopathologic characteristics and patients survival. Loss of E-cadherin was observed in 140 (9.3%) cases and fibronectin was expressed in cancer cells of 320 (21.4%) cases. Twenty three (1.5%) cases were categorized as complete type, 414 (27.6%) as incomplete type (hybrid type, 297; null type, 117), and 1,061 (70.8%) as wild type. Complete EMT phenotype was significantly associated with advanced pT stage, lymph node metastasis, high histological grade, and triple negativity (p < 0.001). Overall survival and disease-free survival rates were significantly worse in the complete type, better in the incomplete type and best in the wild type (p = 0.002 and p < 0.001, respectively). In multivariate Cox proportional hazard model analysis, the complete EMT phenotype was not an independent prognostic factor for both overall and disease-free survival. In conclusion, breast cancer patients with EMT phenotype showed less favorable outcomes than those with wild type as it was strongly associated with clinicopathologic factors indicating aggressive biologic behavior. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-04-07.