EGFR and HER2 Expression in advanced Biliary Tract Cancer

J. Harder; O. Waiz; M. Geissler; H. E. Blum; A. Schmitt-Gräff; O. G. Opitz

doi:10.1055/s-0028-1089488

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

EGFR and HER2 Expression in advanced Biliary Tract Cancer

J Harder ¹, O Waiz ², M Geissler ³, HE Blum ¹, A Schmitt-Gräff ⁴, OG Opitz ⁵

¹Universitätsklinik Freiburg, Medizin II, Tumorzentrum Ludwig Heilmeyer, Freiburg, Germany
²Universitätsklinik Freiburg, Medizin II, Freiburg, Germany
³Städtische Kliniken Esslingen, Gastroenterologie und Onkologie, Esslingen, Germany
⁴Universitätsklinik Freiburg, Pathologisches Institut, Freiburg, Germany
⁵Universitätsklinik Freiburg, Tumorzentrum Ludwig Heilmeyer, Comprehensive Cancer Center Freiburg, Freiburg, Germany

Abstract

Introduction: Patients with biliary tract cancer (BTC) are resectable with curative intent in only approx. 20–30% at time of diagnosis. Advanced BTC has a dismal prognosis with a mean overall survival of 7–8 months. Chemotherapy is widely used with little benefit. New treatment options are therefore needed. Growths factors are involved in the carcinogenesis of various tumortypes and are used as therapeutic targets. Little is known about the pathogenic role and potential therapeutic value of the Epidermal Growth Factor Receptor (EGFR) and the Human Epidermal Growth Factor Receptor 2 (HER2) in advanced BTC.

Methods: Expression of EGFR and HER2 was analyzed in biopsy samples from 124 patients with advanced BTC (51% women, median age 64.8 years), who had been diagnosed 1997–2004. 5µm sections of paraffin embedded tissue had been examined by standard, FDA approved immunohistochemistry and in case of +2 or +3 expression for HER2, by gene amplification (FISH).

Results: 34/124 (27.4%) of the patients had gallbladder cancer, 47/124 (37.9%) had intrahepatic mass forming type and 43/124 (34.7%) extrahepatic or perihilar, intraductal growth type BTC. EGFR expression was examined in 56 samples. EGFR expression was absent in 22/56 (39.3%) of the tumors, the others had expression grade 1 in 12/46 (21.5%), grade 2 in 13/56 (23.2) and grade 3 in 9/56 (16%), respectively. HER2 expression was as follows: 73/124 (58.8%) grade 0, 27/124 (21.8%) grade 1+, 21/124 (17%) grade 2+ and 4/124 (3.2%) grade 3+. HER2 gene amplification was present in 6/124 (5%), 2/21 (10%) of the 2+ positive samples and 4/4 (100%) of the immunhistochemically 3+ biopsies.

Discussion: EGFR and HER2 overexpression has been reported to be present in BTC in up to 81% and 76%, respectively. Like recent data from Japan for resected patients with BTC, our findings for advanced BTC clearly demonstrate a HER2 overexpression and gene amplification in only 10% and 5%, respectively. This discrepancy could be explained by the use of standardized test methods and the fact that large unselected cohorts had not been studied so far. These results suggest that routine testing for HER2 and therapeutic targeting with trastuzumab might not be as promising as initially thought in BTC.