Abstract
207 Background: The entire biliary tree is at risk for malignant change, but little is known about differences in molecular pathogenesis with respect to anatomic site. CEACAM6 is a membrane protein involved in cell adhesion and signaling that is overexpressed in pancreatic adenocarcinoma and associated with poor prognosis. This study examines CEACAM6 expression in the entire spectrum of biliary carcinomas and its relationship to outcome. Methods: Tissue microarrays containing triplicate cores of paraffin-embedded surgical specimens from patients with bile duct carcinoma (hilar, intrahepatic, distal) and control tissue were stained for CEACAM6 by immunohistochemistry. Clinical, pathologic and survival data were analyzed and correlated with CEACAM6 expression. Survival was estimated using the Kaplan-Meier method and compared with log rank test. Results: One hundred twenty cases of bile duct carcinomas from 1992-2007 were assembled in the tissue microarrays. Strong CEACAM6 signal was present in 30/60 (50%) of hilar tumors, 7/45 (16%) of intrahepatic tumors, 7/15 (47%) of distal tumors, and none of the control tissues. Overall median survival and follow-up were 36.4 months and 98.3 months, respectively. CEACAM6 staining did not correlate with sex, grade, positive lymph nodes, vascular invasion or metastases but was associated with age > 65 (p<0.05) and higher T stage (p<0.05). After R0 resection, CEACAM6 expression was associated with disease-specific survival (DSS) only in the subset of patients with intrahepatic cholangiocarcinoma (median DSS 78 months for negative and 16 months for positive, p<0.002). Vascular invasion was the sole independent predictor of survival on multivariate proportional hazards regression (HR=1.742 [1.048-2.895 95%CI], p<0.03) in the entire cohort. Conclusions: CEACAM6 may serve as a marker of poor outcome in patients with intrahepatic cholangiocarcinoma and should be further evaluated as a means of selecting patients for adjuvant therapy after resection.
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