L1 cell adhesion molecule is a novel independent poor prognostic factor of extrahepatic cholangiocarcinoma

Abstract

Purpose: Cholangiocarcinomas (CC) are associatedwith poor survival, but diagnostic markers andth erapeutic targets have not yet been elucidated. We previously found aberrant expression of L1 cell adhesion molecule in intrahepatic CC and a role for L1 in the progression of intrahepatic CC. Here, we analyzedL1 expression in extrahepatic CC (ECC) andevaluatedits prognostic significance. Experimental Design: We examinedL1 expression in tumors from 75 ECC patients by immunohistochemistry. We analyzedthe correlations between L1 expression andclinicopathologic factors as well as patient survival. Results: L1 was not expressedin normal extrahepatic bile duct epithelium but was aberrantly expressedin 42.7% of ECC tumors. High expression of L1 was detectedat the invasive front of tumors andwas significantly associated with perineural invasion (P < 0.01). Univariate analysis indicated that various prognostic factors such as histologic grade 3, advanced pathologic T stage and clinical stage, perineural invasion, nodal metastasis, andhigh expression of L1 were risk factors predicting patient survival. Multivariate analyses done by Cox's proportional hazards model showed that high expression of L1 (hazardratio, 2.171; 95% confidence interval, 1.162-4.055; P = 0.015) and nodal metastasis (hazard ratio, 2.088; 95% confidence interval, 1.159-3.764; P = 0.014) were independent risk factors for patient death. Conclusions: L1 was highly expressedin 42.7% of ECC andits expression was significantly associatedwith perineural invasion. High expression of L1 andnod al metastasis were independent poor prognostic factors predicting overall survival in patients with ECC.