Differences in immunohistochemical biomarkers between intra- and extrahepatic cholangiocarcinoma: a systematic review and meta-analysis.
OBJECTIVE
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.
Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
Jimme K
JK
Wiggers
Anthony T
AT
Ruys
Bas
B
Groot Koerkamp
Ulrich
U
Beuers
Fiebo J
FJ
ten Kate
Thomas M
TM
van Gulik
D001650:Bile Duct Neoplasms / Q000175:diagnosis*; D017734:Bile Ducts, Extrahepatic; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000032:analysis*; D018281:Cholangiocarcinoma / Q000175:diagnosis*; D015331:Cohort Studies; D016206:Databases, Bibliographic; D066246:ErbB Receptors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D058990:Molecular Targeted Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human
biomarkers; cholangiocarcinoma; extrahepatic; immunohistochemistry; intrahepatic