title: HER2 in situ hybridization in gastric and gastroesophageal adenocarcinoma: comparison of automated dual ISH to FISH.
abstract: Patients with gastric and gastroesophageal junction (GEJ) adenocarcinomas that are HER2 positive by immunohistochemistry (IHC) or in situ hybridization show a significant survival benefit with trastuzumab therapy. In situ hybridization is traditionally done by fluorescence in situ hybridization (FISH), despite some limitations. An alternative is the dual in situ hybridization (Dual ISH) technique that is fully automated and uses differentially labeled CEP17 and HER2 probes that can be read by light microscopy on 1 slide. The aim of this study was to assess the utility of Dual ISH in gastric/GEJ cancer and to compare the results with those obtained by IHC and FISH. Cases of gastric/GEJ adenocarcinoma were analyzed by IHC, FISH, and Dual ISH and the correlation between methods calculated. Results for 50 patients were available. There was a 98% (49/50) concordance rate between Dual ISH and FISH. One discrepant case was nonamplified by FISH but showed focal amplification by Dual ISH. Discrepancy was attributed to tumor heterogeneity, which was a frequent finding (78% of HER2-positive cases). There was excellent correlation between Dual ISH and FISH for assessment of HER2 amplification. Dual ISH was rapid, easy to interpret, and maintained cell morphology, which was valuable in identifying tumor heterogeneity.
authors: *Department of Medical Oncology, St. Michael's Hospital and University of Toronto, Toronto, ON, Canada †Department of Laboratory Medicine, the Li Ka Shing Knowledge Institute.
authors: Andrea
authors: A
authors: Grin
authors: Christine
authors: C
authors: Brezden-Masley
authors: Sharon
authors: S
authors: Bauer
authors: Catherine J
authors: CJ
authors: Streutker
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D057205:Automation, Laboratory; D014408:Biomarkers, Tumor / Q000235:genetics*; D002503:Centromere / Q000737:chemistry; D002886:Chromosomes, Human, Pair 17; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004943:Esophagogastric Junction / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human