Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival.
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.
Varga
Meri
M
Division of Hematology and Oncology, University of Innsbruck, Innsbruck, Austria.
Obrist
Peter
P
Schneeberger
Stephan
S
Mühlmann
Gilbert
G
Felgel-Farnholz
Christina
C
Fong
Dominic
D
Zitt
Mathias
M
Brunhuber
Thomas
T
Schäfer
Georg
G
Gastl
Guenther
G
Spizzo
Gilbert
G
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
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule