title: Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation.
abstract: Amplification and overexpression of ErbB2 (Her2) is a frequent event in oesophageal adenocarcinomas. Assessment of ErbB2 status is crucial for identifying patients who are likely to benefit from treatment with trastuzumab. In this study, we performed a comprehensive analysis of ErbB2 amplification and expression in 142 oesophageal adenocarcinomas by comparing the most commonly used methods for ErbB2 assessment: ErbB2 expression was determined by immunohistochemistry and was scored (0, 1+, 2+ and 3+) according to a recently described modified scoring system for gastric cancer. ErbB2 amplification was evaluated by bright field double in situ hybridisation. The results were compared with pathologic features, patients' survival and previously published data from fluorescence in situ hybridisation analysis. On the basis of immunohistochemistry, which was applicable in 110 cores of the cases, 83 tumours (75%) had a score of 0 or 1+ (immunohistochemistry negative), 13 tumours (12%) were scored as 2+ and 14 tumours (13%) were scored as 3+. In situ hybridisation data were obtained from 142 cases. There was a highly significant correlation of immunohistochemistry, bright field in situ hybridisation and fluorescent in situ hybridisation (P<0.001 each). In total, 41 tumours (29%) were categorised as ErbB2 positive, which was defined as immunohistochemistry 3+ and/or an ErbB2/Chr17 quotient of ≥2 as assessed by either bright field double in situ hybridisation or fluorescence in situ hybridisation. ErbB2 positivity was observed more frequently in tumours with lower differentiation grades (P=0.029). Patients with ErbB2-positive tumours had a significantly worse prognosis, both in univariate analysis (P=0.004) and in multivariate analysis (P=0.03). In conclusion, we demonstrate that a significant number of oesophageal adenocarcinomas are positive for ErbB2. Assessment of ErbB2 amplification can be equivalently performed by conventional fluorescence in situ hybridisation or other light-microscopy-based methods, such as the novel bright field double in situ hybridisation technique.
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany. rupert.langer@lrz.tu-muenchen.de
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.forename: Sandra
authors.initials: S
authors.lastname: Rauser
authors.forename: Marcus
authors.initials: M
authors.lastname: Feith
authors.forename: Jörg M
authors.initials: JM
authors.lastname: Nährig
authors.forename: Annette
authors.initials: A
authors.lastname: Feuchtinger
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases