Abstract P6-01-17: Epithelial paradox; clinical significance of co-expression of E-cadherin and vimentin in the invasion and the metastasis of breast cancer

Abstract Background: E-cadherin and vimentin are now regarded as major and conventional canonical markers of epithelial-mesenchymal transition (EMT). It is commonly assumed E-cadherin is uniformly lost during the process of EMT. We previously reported that the elevated expression of vimentin contributes to the aggressive phenotype in invasive breast cancer. On the other hand, the role of E-cadherin in breast cancer biology might be unclear and more complex. Although, cell cohesion during breast cancer invasion is often overlooked, accumulating evidences indicate breast tumor cells are typically cohesive and often display membrane-localized E-cadherin in both the primary tumor and distant metastases, termed collective invasion. Multiple mechanisms have emerged to address how epithelial breast tumors invade. Aims: The aim of this study is to reveal the clinical importance of the expression pattern of E-cadherin and vimentin in breast cancer. Methods: The E-cadherin and vimentin protein expression were evaluated by immunohistochemistry (IHC) in 177 invasive breast cancer samples. Among these, E-cadherin and vimentin expression were evaluated in the set of primary breast cancer and metastatic lymph nodes in 65 cases. In addition, E-cadherin and vimentin expression were analyzed by immunofluorescent staining and evaluated using confocal laser scanning microscopy to see E-cadherin and vimentin localization in the breast cancer cells. Results: The positive vimentin expression was highly correlated with poor disease-free survival (DFS) and overall survival (OS) (p=0.019 and p=0.0044), however, the E-cadherin expression alone did not correlate with prognosis. Interestingly, both E-cadherin and vimentin positive tumors had the worst DFS and OS among all breast cancer (p=0.03 and p=0.0089). Vimentin expression was highly correlated between primary tumors and metastatic lymph nodes. However, E-cadherin expression levels were significantly elevated in metastatic lymph nodes (p=0.0017). Co-expression of E-cadherin and vimentin in the metastatic lymph nodes also showed worst DFS and OS (p=0.12 and p=0.027).Immunofluorescent analysis revealed that E-cadherin and vimentin were co-localized within the same tumor cells in many of the E-cadherin high/vimentin positive tumors. Conclusions: Co-expression of E-cadherin and vimentin seems to be associated with the most aggressive phenotype and poorest prognosis in breast cancer. Moreover, co-localization of E-cadherin and vimentin within the same breast cancer cells suggests the significance of the expressions of both proteins in breast cancer invasion and metastasis. Citation Format: Yamashita N, Tokunaga E, Inoue Y, Tanaka K, Saeki H, Oki E, Maehara Y. Epithelial paradox; clinical significance of co-expression of E-cadherin and vimentin in the invasion and the metastasis of breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-17.