title: HER2 status in gastric/gastro-oesophageal junctional cancers: should determination of gene amplification by SISH use HER2 copy number or HER2: CEP17 ratio?
abstract: The aim of this study was to compare HER2 amplification, as determined by the HER2 copy number (CN) and the HER2/CEP17 ratio, with protein expression in gastric and gastro-oesophageal junction (G/GOJ) adenocarcinoma.HER2 immunohistochemistry (IHC) and silver in situ hybridisation (SISH) were performed in 185 cases. Modified gastric criteria were used for IHC scoring. HER2 and CEP17 CNs were counted in at least 20 cancer cells and the ratio calculated as per previously defined protocols. These two SISH methods were statistically compared against the different IHC scores.Thirty-four cases showed amplification, by both methods in 29, and either method in five. IHC score was 3+ in 29 cases; 26 showed amplification by both methods, one by ratio only and two were not amplified. IHC score was 2+ in 24 cases; three showed amplification by both methods and two by either. One each of IHC 1+ and 0 showed an increased ratio but not CN. The HER2 CN and ratio for IHC score 3+ compared to scores 2+, 1+ and 0 were significantly different (all p < 0.01). The CN for IHC 2+ vs IHC 1+ and IHC 0 was significantly different (both p < 0.01) but the ratio was not (p = 0.5711 and p = 0.2857, respectively). The CN and the ratio for scores 1+ and 0 were not significantly different (p = 0.9823 and p = 0.9910, respectively).The HER2 CN differentiates between the different IHC scores better than the HER2:CEP17 ratio. Cases that show IHC3+ and high CN may not require calculation of the ratio. Furthermore, consideration should be given to the CN when IHC negative cases appear amplified by the ratio only.
authors.affiliation: 1PathWest Laboratory Medicine, Perth 2School of Pathology and Laboratory Medicine, University of Western Australia, Perth 3School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, WA 4Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne 5Department of Pathology and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic, Australia.
authors.forename: Marian Priyanthi
authors.initials: MP
authors.lastname: Kumarasinghe
authors.forename: Willem Bastiaan
authors.initials: WB
authors.lastname: de Boer
authors.forename: Tze Sheng
authors.initials: TS
authors.lastname: Khor
authors.forename: Esther M
authors.initials: EM
authors.lastname: Ooi
authors.forename: Nic
authors.initials: N
authors.lastname: Jene
authors.forename: Sureshini
authors.initials: S
authors.lastname: Jayasinghe
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002503:Centromere / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004943:Esophagogastric Junction; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060787:Neoplasm Grading; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human