Abstract P2-10-39: Does E-cadherin or N-cadherin or epithelial-mesenchymal transition have a probability of clinical implication of the prognostic marker in invasive ductal carcinoma?

Abstract

Abstract Purpose: Epithelial to mesenchymal transition (EMT) is widely accepted hypothesis of progression and metastasis in carcinoma. EMT can be explained as a loss of epithelial features and gain of mesenchymal properties, and in the same manner, it can be characterized by down-regulation of epithelial cellular markers, such as E-cadherin (EC) and up-regulation of mesenchymal cellular markers, such as N-cadherin (NC). Breast cancer has a diverse clinical spectrum, treatments and prognosis according to clinicopathologic characteristics and immunohistochemical features. Identifying the presence of EMT also would be able to predict the prognosis and design better and customized therapy. Our objective was to evaluate expression of the EC/NC and EMT and correlation between EMT and clinicopathologic, immunohistochemical features and to investigate clinical implication of the EC/NC and EMT as prognostic marker in breast cancer. Methods: Using the clinicopathologic data of 480 patients who underwent operation for invasive ductal carcinoma (IDC) during February 2001 to December 2008. 282 patients with good quality of paraffin embedded tissue block were selected. The ER and PR immunohistochemistry was scored using the Allred Score. EC and NC expression were classified on the basis of intensity of immunohistochemistry staining. The gain of a mesenchymal marker or loss of an epithelial marker was interpreted as EMT-positive. In this study, breast cancer was classified into four types according to the immunohistochemical expression of ER, PR and HER2 expression on immunohistochemical analysis and/or with HER2 gene by FISH analysis: luminal A, luminal B, HER2-enriched, and triple negative type. Results: Median follow-up period was 52.6 months (range 1–113) and median age was 49 years (range 27–79). Of total 282 cases, 152 (53.9%) cases were classified as luminal A, 32 (11.3%) classified as luminal B, 43 (15.2%) cases were HER2-enriched and 55 (19.5%) cases were triple negative type. Expression of a mesenchymal marker, NC was observed in 22 (7.8%) patients and loss of an epithelial marker, EC was observed in 57 (20.2%) cases. A total of 75 (26.6%) were interpreted as EMT-positive. NC score was associated with HER2-enriched, and triple negative molecular subtype (P = 0.0234). NC status was associated with HER2 positive status (P = 0.0456) and HER2-enriched, triple negative molecular subtype (P = 0.0029). EMT correlated with ER negative status (P = 0.0199). T stage (P < 0.001), N stage (P < 0.001) and TNM stage (P < 0.001) and ER (P = 0.0403) and PR (P = 0.0041) status significantly influenced disease-free survival (DFS). Age (P = 0.0185) and T stage (P = 0.0017), N stage (P < 0.001) and ER (P = 0.0048), and PR status (P = 0.0072), molecular subtype (P = 0.0372), significantly influenced overall survival (OS). The status of the EC/NC and EMT did not significantly affect DFS or OS. Conclusion: NC status was associated with HER2 positive status and HER2-enriched, triple negative molecular subtype. And EMT correlated with ER negative status. EC/NC and EMT status have relevance to a specific molecular subtype or a probability of clinical implication of the poor prognostic marker in breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-39.