Ep-CAM RNA expression predicts metastasis-free survival in three cohorts of untreated node-negative breast cancer

Abstract

Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention as a prognostic factor in breast cancer. We aimed to validate the influence of Ep-CAM RNA expression in untreated node-negative breast cancer. Ep-CAM RNA expression was evaluated utilizing microarray-based gene-expression profiling in 194 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. The prognostic significance of Ep-CAM RNA expression for disease-free survival (DFS), metastasis-free survival (MFS), and breast cancer-specific overall survival (OS) was evaluated in univariate and multivariate analysis adjusted for age, grading, pTstage, ER as well as PR receptor and HER-2 status. Additionally, Ep-CAM RNA expression was compared with immunohistochemistry (IHC) for Ep-CAM in 194 patients. The prognostic impact of Ep-CAM gene expression was validated in further 588 node-negative breast cancer patients. Levels of Ep-CAM RNA expression showed a significant correlation with IHC (P=0.001) and predicted in univariate analysis DFS (P=0.001, HR=2.4), MFS (P=0.003, HR=2.5), and OS (P=0.002, HR=3.1) accurately. The prognostic influence of Ep-CAM RNA was significant also in multivariate analysis for DFS (P=0.017, HR=2.0), MFS (P=0.049, HR=1.9), and OS (P=0.042, HR=2.3), respectively. The association with MFS was confirmed in an independent validation cohort in univariate (P=0.006, HR=1.9) and multivariate (P=0.035, HR=1.7) analysis. Ep-CAM RNA correlated with the proliferation metagene (P<0.001, R=0.425) Nevertheless, in multivariate analysis, Ep-CAM was associated with MFS independent from the proliferation metagene (P=0.030, HR=1.8). In conclusion, Ep-CAM RNA expression is associated with poor MFS in three cohorts of untreated node-negative breast cancer.