Brief Article
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World J Gastroenterol. Dec 28, 2013; 19(48): 9334-9342
Published online Dec 28, 2013. doi: 10.3748/wjg.v19.i48.9334
Inhibitor of differentiation proteins do not influence prognosis of biliary tract cancer
Jan Harder, Michael J Müller, Matthias Fuchs, Vera Gumpp, Annette Schmitt-Graeff, Richard Fischer, Melanie Frank, Oliver Opitz, Jens Hasskarl
Jan Harder, Department of Gastroenterology, Hematology and Oncology, Hegau-Bodensee-Hochrhein Kliniken, 78221 Singen, Germany
Michael J Müller, Jens Hasskarl, Department of Hematology and Oncology, University Medical Center Freiburg, 79104 Freiburg, Germany
Michael J Müller, Matthias Fuchs, Vera Gumpp, Oliver Opitz, Comprehensive Cancer Center Freiburg, Tumorzentrum Ludwig Heilmeyer, University Medical Center Freiburg, 79104 Freiburg, Germany
Annette Schmitt-Graeff, Institute of Pathology, University Medical Center Freiburg, 79104 Freiburg, Germany
Richard Fischer, Onkologie Dreiländereck, 79539 Lörrach, Germany
Melanie Frank, iOMEDICO AG Freiburg, 79108 Freiburg im Breisgau, Germany
Author contributions: Hasskarl J, Müller MJ and Harder J designed the research; Hasskarl J, Müller MJ, Fuchs M, Harder J and Schmitt-Graeff A performed the research; Gumpp V, Frank M, Opitz O, Hasskarl J, Müller MJ and Harder J analyzed the data; Hasskarl J, Müller MJ, Fischer R, Opitz O and Harder J wrote the manuscript; Harder J and Müller MJ contributed equally to this work.
Correspondence to: Jan Harder, MD, Department of Gastroenterology, Hematology and Oncology, Hegau-Bodensee-Hochrhein Kliniken, Virchowstraße 10, 78221 Singen, Germany. jan.harder@hbh-kliniken.de
Telephone: +49-7731-892700 Fax: +49-7731-892705
Received: May 2, 2013
Revised: September 15, 2013
Accepted: September 29, 2013
Published online: December 28, 2013
Processing time: 257 Days and 18.7 Hours
Abstract

AIM: To investigate the expression and clinical relevance of inhibitor of differentiation (ID) proteins in biliary tract cancer.

METHODS: ID protein expression was analyzed in 129 samples from patients with advanced biliary tract cancer (BTC) (45 extrahepatic, 50 intrahepatic, and 34 gallbladder cancers), compared to normal controls and correlated with clinical an pathological parameters.

RESULTS: ID1-3 proteins are frequently overexpressed in all BTC subtypes analyzed. No correlation between increased ID protein expression and tumor grading, tumor subtype or treatment response was detected. Survival was influenced primary tumor localization (extrahepatic vs intrahepatic and gall bladder cancer, OS 1.5 years vs 0.9 years vs 0.7 years, P = 0.002), by stage at diagnosis (OS 2.7 years in stage I vs 0.6 years in stage IV, P < 0.001), resection status and response to systemic chemotherapy. In a multivariate model, ID protein expression did not correlate with clinical prognosis. Nevertheless, there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression (P = 0.076).

CONCLUSION: ID protein expression is frequently deregulated in BTC but does not influence clinical prognosis. Their usefulness as prognostic biomarkers in BTC is very limited.

Keywords: Biliary tract cancer; Cholangiocarcinoma; Inhibitor of differentiation; Prognostic factors

Core tip: Cholangiocarcinoma present as heterogeneous tumors with generally poor prognosis. Molecular changes that drive tumor development are poorly understood, and no valid prognostic markers other than stage and performance status have been identified. Here we analyzed the protein expression of the four inhibitor of differentiation (ID)-proteins by immunohistochemistry in 129 patients with advanced biliary tract cancer, which showed a deregulated ID protein expression in cancer cells and this protein expression partly correlated with the overall survival of patients. Therefore the ID-proteins maybe useful prognostic markers.