Epidermal growth factor receptor (EGFR) status and prognosis in gallbladder cancer.

Abstract

e14657 Background: Studies from USA, Asia and Australia showed EGFR over-expression in gallbladder cancer (GC), and recent case reports suggest a role for EGFR targeted therapies in this disease. Methods: We studied the prognostic role of EGFR expression and its association with clinicopathologic features in forty-two GC patients surgically treated at our center, from 1995 to 2006. None received targeted cancer therapeutics. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic biliary epithelia were obtained and assessed for immunohistochemical (IH) expression of EGFR, cyclo-oxygenase-2 (COX2), E-cadherin and p53 protein. Nonparametric correlations were assessed by Spearman’s rho; survival analysis was performed using the Kaplan-Meier method and Cox regression; and p-values were computed for two-tailed tests. Results: EGFR IH scores 0, +1, +2, and +3 were observed in 48.7%, 23.1%, 17.9%, and 10.3%, respectively. They were correlated with p53 staining (rho=0.48; p=0.002); T-stage (rho=0.38; p=0.016); serum CA-19.9 (rho=0.48; p=0.016); and serum CEA (rho=0.56; p=0.004). Median overall survival (OS) was 8.0 months (95% C.I.: 5.6 to 10.3); 1-year and 2-year survival rates were 43.7% and 23.5%, respectively. OS were 18.0 months, 14.0 months, and 4.0 months for tumors with 0, 1+ and 2+ to 3+ EGFR staining, respectively. Univariate analysis suggested a worse prognostic significance for low serum albumin (p=0.001); elevated CEA (p=0.007) and CA-19.9 (p=0.007) levels; positive surgical margins (p=0.001); gallbladder fundus tumors (p=0.007); histologic grade 3 (p=0.003); positive nodes (p=0.001); lymphovascular invasion (p=0.001); tumoral necrosis (p=0.004); perineural invasion (p=0.002); and EGFR expression (p=0.004). In the multivariate analysis, low serum albumin (p=0.006), tumoral necrosis (p<0.001) and EGFR expression (p<0.001) predicted poor OS. Conclusions: We found tumor immunoreactivity for EGFR in nearly half of the cases and it was independently associated with poor survival in GC patients.