Differences in immunohistochemical biomarkers between intra- and extrahepatic cholangiocarcinoma: A systematic review and meta-analysis

Background and Aim: Cholangiocarcinomas of different locations differ in growth patterns, symptoms, treatment response, and survival. Still, they are regarded in many studies as a uniform malignancy. Because intra- (iCCA) and extrahepatic (eCCA) cholangiocarcinoma display such differences, we performed a systematic review and meta-analysis to analyze differences in the immunohistochemical profile of these tumors. Methods: In February 2014, we searched the two main medical literature databases MEDLINE and EMBASE. We extracted risk ratios and 95% confidence intervals from the identified studies and performed random-effects model meta-analyses in accordance with PRISMA and REMARK guidelines. Results: A total of 54 cohort studies, including 4458 patients and studying 102 individual markers met the inclusion criteria. Of the 57 markers that were evaluated in more than 30 iCCA and eCCA patients, 18 showed a statistically significant difference in expression between iCCA and eCCA. Biomarkers expressed differently between iCCA and eCCA included potential targets of therapy: EGFR, c-erbB-2 and VEGF-A. Several markers showed no statistical difference but large 95% confidence intervals, suggesting insufficient sample size. Conclusions: This systematic review shows differences in marker expression between iCCA and eCCA. Consequently, patients with iCCA and eCCA may benefit from different treatment strategies.