title: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131, Mainz, Germany. marcus.schmidt@frauen.klinik.uni-mainz.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
authors.forename: Ilka Brigitte
authors.initials: IB
authors.lastname: Petry
authors.forename: Daniel
authors.initials: D
authors.lastname: Böhm
authors.forename: Antje
authors.initials: A
authors.lastname: Lebrecht
authors.forename: Christian
authors.initials: C
authors.lastname: von Törne
authors.forename: Susanne
authors.initials: S
authors.lastname: Gebhard
authors.forename: Aslihan
authors.initials: A
authors.lastname: Gerhold-Ay
authors.forename: Cristina
authors.initials: C
authors.lastname: Cotarelo
authors.forename: Marco
authors.initials: M
authors.lastname: Battista
authors.forename: Wiebke
authors.initials: W
authors.lastname: Schormann
authors.forename: Evgenia
authors.initials: E
authors.lastname: Freis
authors.forename: Silvia
authors.initials: S
authors.lastname: Selinski
authors.forename: Katja
authors.initials: K
authors.lastname: Ickstadt
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.forename: Martin
authors.initials: M
authors.lastname: Sebastian
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.forename: Heinz
authors.initials: H
authors.lastname: Koelbl
authors.forename: Mathias
authors.initials: M
authors.lastname: Gehrmann
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D049109:Cell Proliferation; D015331:Cohort Studies; D018572:Disease-Free Survival; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D012313:RNA / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D012313:RNA