title: Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival.
abstract: OBJECTIVE
  Gallbladder carcinoma is an aggressive type of cancer that is difficult to cure by conventional procedures. There thus is a need to identify novel molecular markers for the assessment of prognosis and as potential therapeutic targets. This retrospective study was designed to investigate the prognostic significance of epithelial cell adhesion molecule (Ep-CAM) overexpression in human gallbladder carcinoma.
  
  
  METHODS
  Ep-CAM expression was examined immunohistochemically on paraffin-embedded tissue specimens from 99 patients who underwent surgical treatment for gallbladder carcinoma in the period between August 1988 and May 1999.
  
  
  RESULTS
  Ep-CAM overexpression was found in 63 (63.6%) of the tumor samples. Kaplan-Meier curves showed that Ep-CAM overexpression was significantly related to decreased overall survival (P < 0.01). Overall survival gradually worsened with increasing Ep-CAM scores. Notably, in the subgroup of pT1 tumors (n = 17), patients without Ep-CAM overexpression had a 5-year overall survival rate of 100% compared with 38% (P = 0.01) for patients with Ep-CAM-overexpressing tumors. By univariate analysis, no correlation was found with conventional clinicopathological parameters. Multivariate analysis, including Ep-CAM expression, pT stage, tumor grade, and resection margin involvement, showed that Ep-CAM overexpression was an independent prognostic marker in gallbladder carcinoma (P = 0.03; relative risk, 1.8).
  
  
  CONCLUSIONS
  These results demonstrate for the first time that Ep-CAM overexpression is an independent prognostic marker in gallbladder carcinoma and that its prognostic impact should be validated prospectively. Furthermore, the Ep-CAM antigen represents an attractive target for specific therapies with monoclonal antibodies or specific vaccines in patients with Ep-CAM-overexpressing gallbladder carcinoma.
authors.affiliation: Division of Hematology and Oncology, University of Innsbruck, Innsbruck, Austria.
authors.forename: Meri
authors.initials: M
authors.lastname: Varga
authors.forename: Peter
authors.initials: P
authors.lastname: Obrist
authors.forename: Stephan
authors.initials: S
authors.lastname: Schneeberger
authors.forename: Gilbert
authors.initials: G
authors.lastname: Mühlmann
authors.forename: Christina
authors.initials: C
authors.lastname: Felgel-Farnholz
authors.forename: Dominic
authors.initials: D
authors.lastname: Fong
authors.forename: Mathias
authors.initials: M
authors.lastname: Zitt
authors.forename: Thomas
authors.initials: T
authors.lastname: Brunhuber
authors.forename: Georg
authors.initials: G
authors.lastname: Schäfer
authors.forename: Guenther
authors.initials: G
authors.lastname: Gastl
authors.forename: Gilbert
authors.initials: G
authors.lastname: Spizzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005706:Gallbladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule