Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Sep 28, 2009; 15(36): 4511-4517
Published online Sep 28, 2009. doi: 10.3748/wjg.15.4511
EGFR and HER2 expression in advanced biliary tract cancer
Jan Harder, Oliver Waiz, Florian Otto, Michael Geissler, Manfred Olschewski, Brigitte Weinhold, Hubert E Blum, Annette Schmitt-Graeff, Oliver G Opitz
Jan Harder, Oliver Waiz, Hubert E Blum, Department of Medicine II, University Medical Center, D-79106 Freiburg, Germany
Jan Harder, Oliver Waiz, Hubert E Blum, Annette Schmitt-Graeff, Oliver G Opitz, Tumorzentrum Ludwig Heilmeyer-Comprehensive Cancer Center Freiburg, D-79106 Freiburg, Germany
Florian Otto, Tumorzentrum ZeTuP, St. Gallen, Switzerland, and Department of Medicine I, University Medical Center, D-79106 Freiburg, Germany
Michael Geissler, Department of Medicine, Gastroenterology and Oncology, Municipal Hospital Esslingen, Germany
Manfred Olschewski, Department of Medical Biometry und Statistics, University of Freiburg, D-79106 Freiburg, Germany
Brigitte Weinhold, Annette Schmitt-Graeff, Institute of Pathology, University Medical Center, D-79106 Freiburg, Germany
Author contributions: Harder J and Waiz O contributed equally to this work; Harder J, Waiz O, Geissler M and Opitz OG designed research; Harder J, Waiz O, Weinhold B and Schmitt-Graeff A performed research; Harder J, Waiz O, Olschewski M, Otto F and Schmitt-Graeff A analyzed the data; Harder J, Otto F, Blum HE and Opitz OG wrote the paper.
Supported by (In part) Hoffmann la Roche AG, Grenzach-Whylen, Germany
Correspondence to: Dr. Jan Harder, Department of Medicine II, University Medical Center, Hugstetter Str. 55, D-79106 Freiburg, Germany. jan.harder@uniklinik-freiburg.de
Telephone: +49-761-2703401 Fax: +49-761-2703550
Received: May 1, 2009
Revised: September 2, 2009
Accepted: September 9, 2009
Published online: September 28, 2009

AIM: To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancer (BTC).

METHODS: EGFR and HER2 expression was studied in biopsy samples from 124 patients (51% women; median age 64.8 years), with advanced BTC diagnosed between 1997 and 2004. Five micrometers sections of paraffin embedded tissue were examined by standard, FDA approved immunohistochemistry. Tumors with scores of 2+ or 3+ for HER2 expression on immunochemistry were additionally tested for HER2 gene amplification by fluorescence in situ hybridisation (FISH).

RESULTS: 34/124 patients (27.4%) had gallbladder cancer, 47 (37.9%) had intrahepatic BTC and 43 (34.7%) had extrahepatic or perihilar BTC. EGFR expression was examined in a subset of 56 samples. EGFR expression was absent in 22/56 tumors (39.3%). Of the remaining samples expression was scored as 1+ in 12 (21.5%), 2+ in 13 (23.2%) and 3+ in 9 (16%), respectively. HER2 expression was as follows: score 0 73/124 (58.8%), score 1+ 27/124 (21.8%), score 2+ 21/124 (17%) and score 3+ 4/124 (3.2%). HER2 gene amplification was present in 6/124, resulting in an overall amplification rate of 5%.

CONCLUSION: Our data suggest that routine testing and therapeutic targeting of HER2 does not seem to be useful in patients with BTC, while targeting EGFR may be promising.

Keywords: Cholangiocarcinoma, Gallbladder cancer, Chemotherapy, Targeted therapy