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

• DOI: 10.1007/s00428-010-0952-2
• Publication Date: 2010-07-27T11:46:14Z
• Authors: Josef Rüschoff; Manfred Dietel; Gustavo Baretton; Susanne Arbogast; Axel Walch; Geneviéve Monges; Marie-Pierre Chenard; Frédérique Penaul...; Iris Nagelmeier; Werner Schlake; H. Höfler; H. H. Kreipe
• Keywords: Concordance; Tissue microarray; Guideline; Targeted Therapy; Stomach cancer

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