Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma

Background. Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. Patients and methods. We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. Results. Tumours were scored as high and low/absent expressers (≥50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P = 0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P < 0.001). Vascular invasion was related to tumour recurrence (P = 0.025) and to decreased disease free survival (P < 0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P = 0.01). Conclusions. Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion. © 2004 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserve