Abstract P5-04-03: Epithelial-mesenchymal transition is associated with in situ to invasive transition of basal-like breast cancer

Abstract

Abstract BACKGROUND: Epithelial-mesenchymal transition (EMT) is known to play an important role in breast cancer invasion and metastatic progression and to be associated with cancer stem cells and basal-like subtype. However, its role in the progression of in situ to invasive breast carcinoma is uncertain. To investigate this question, we evaluated the difference in the expression of EMT-related markers between pure ductal carcinoma in situ (DCIS) and invasive carcinomas according to molecular subtype. METHODS: We performed immunohistochemical analyses of EMT-related markers [expression of vimentin, smooth muscle actin (SMA), osteonectin and N-cadherin, translocation of β-catenin and loss of E-cadherin] and breast cancer stem cell markers (CD44+/CD24−, ALDH1) in 320 invasive carcinomas and 179 pure DCIS of breast using tissue microarrays. We also analyzed 39 basal-like invasive cancers with adjacent DCIS component to determine the difference in the expression of EMT-related markers in the invasive and DICS component within individual cases. RESULTS: In invasive carcinomas, vimentin, SMA and osteonectin were highly expressed in basal-like subtype. In addition, loss of E-cadherin and translocation of β-catenin were most frequently found in basal-like subtype. Furthermore, there were positive correlations between the expression of EMT-related markers and stem cell markers (CD44+/CD24- and ALDH1). However, there was no significant difference in the expression of EMT-related markers according to molecular subtype in pure DCIS. When comparing invasive carcinoma with pure DCIS, expression of EMT-related markers was significantly higher in invasive carcinoma than in pure DCIS. Subgroup analysis revealed higher expression of EMT-related markers in invasive carcinoma than in DCIS in basal-like subtype, but not in non-basal-like subtypes. Moreover, in 39 basal-like invasive cancers with adjacent DCIS, expression of mesenchymal markers was increased in invasive component compared to DCIS component. CONCLUSIONS: Our study confirmed that EMT is an intrinsic characteristic of basal-like subtype and is associated with breast cancer with stem cell phenotype. However, increased expression of EMT-related markers in invasive carcinoma compared to pure DCIS, especially in basal-like subtype, and in the invasive component of basal-like invasive carcinoma with DCIS component also suggests a role of EMT in the transition of in situ- to invasive carcinoma in basal-like breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-04-03.