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Open Access 01-09-2010 | Original Article

HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing

Authors: Josef Rüschoff, Manfred Dietel, Gustavo Baretton, Susanne Arbogast, Axel Walch, Geneviéve Monges, Marie-Pierre Chenard, Frédérique Penault-Llorca, Iris Nagelmeier, Werner Schlake, H. Höfler, H. H. Kreipe

Published in: Virchows Archiv | Issue 3/2010

Abstract

Trastuzumab-based therapy has been shown to confer overall survival benefit in HER2-positive patients with advanced gastric cancer in a large multicentric trial (ToGA study). Subgroup analysis identified adenocarcinomas of the stomach and gastroesophageal (GE) junction with overexpression of HER2 according to immunohistochemistry (IHC) as potential responders. Due to recent approval of trastuzumab for HER2 positive metastatic gastric and GE-junction cancer in Europe (EMEA) HER2 diagnostics is now mandatory with IHC being the primary test followed by fluorescence in situ hybridization (FISH) in IHC2+ cases. However, in order to not miss patients potentially responding to targeted therapy determination of a HER2-positive status for gastric cancer required modification of scoring as had been proposed in a pre-ToGA study. To validate this new HER2 status testing procedure in terms of inter-laboratory and inter-observer consensus for IHC scoring a series of 547 gastric cancer tissue samples on a tissue microarray (TMA) was used. In the first step, 30 representative cores were used to identify specific IHC HER2 scoring issues among eight French and German laboratories, while in the second step the full set of 547 cores was used to determine IHC HER2 intensity and area score concordance between six German pathologists. Specific issues relating to discordance were identified and recommendations formulated which proved to be effective to reliably determine HER2 status in a prospective test series of 447 diagnostic gastric cancer specimens.

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Title: HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing
Authors: Josef Rüschoff
Manfred Dietel
Gustavo Baretton
Susanne Arbogast
Axel Walch
Geneviéve Monges
Marie-Pierre Chenard
Frédérique Penault-Llorca
Iris Nagelmeier
Werner Schlake
H. Höfler
H. H. Kreipe
Publication date: 01-09-2010
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 3/2010
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-010-0952-2

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HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing

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