PMID- 33144857 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220418 IS - 1687-8450 (Print) IS - 1687-8469 (Electronic) IS - 1687-8450 (Linking) VI - 2020 DP - 2020 TI - HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies. PG - 8860174 LID - 10.1155/2020/8860174 [doi] LID - 8860174 AB - BACKGROUND: Although amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) is used as an indicator for response to trastuzumab, the reported response rate is low, and few patients with gastric cancer (GC) benefit from this individualized therapy. The aim of this study was to examine the expression of c-erbB-2 oncoprotein (HER2), in GC samples, using two commercial immunohistochemical (IHC) antibodies, and to validate the results by checking HER2 gene amplification by fluorescence in situ hybridization (FISH). METHODS: We assessed the IHC expression of HER2 using the polyclonal antibody from Dako and CB11 clone from Leica, in 93 consecutive cases of GC samples. In all of the cases, FISH analysis was also performed using the BOND-MAX platform. RESULTS: No significant difference was observed between the two HER2 antibodies. Of the 93 cases, 22.58% demonstrated at least focal and 1+ HER2 positivity. Seven cases (7.53%) exhibited 3+ expression, and another 7 carcinomas (7.53%) were equivocal (2+). HER2 amplification was seen in 11 cases (11.83%), 10 of which were differentiated adenocarcinomas. In 5 of the cases, 2-5 sections were examined, which proved the extremely high intratumorally/intraglandular heterogeneity. FISH heterogeneity was higher in cases with only 2+ positivity on IHC assessment, compared with those showing at least one small focus of 3+ overexpression. HER2 amplification proved to be an independent negative prognostic factor. CONCLUSIONS: Due to the highly heterogeneous aspect of GC, at least 3-4 slides should be assessed by IHC, before considering a tumor to be HER2-negative. In cases with small 3+ foci representing less than 5% of tumor and in equivocal (2+) cases, FISH analysis remains the gold standard method. CI - Copyright (c) 2020 Catalin Bogdan Satala et al. FAU - Satala, Catalin Bogdan AU - Satala CB AD - Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu-Mures, Romania. AD - Department of Pathology, Clinical County Emergency Hospital, Targu-Mures, Romania. FAU - Jung, Ioan AU - Jung I AD - Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu-Mures, Romania. FAU - Stefan-van Staden, Raluca Ioana AU - Stefan-van Staden RI AD - Laboratory of Electrochemistry and PATLAB, National Institute of Research for Electrochemistry and Condensed Matter, Bucharest, Romania. FAU - Kovacs, Zsolt AU - Kovacs Z AD - Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Tirgu-Mures, Romania. FAU - Molnar, Calin AU - Molnar C AD - Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Tirgu-Mures, Romania. AD - Department of Surgery, Clinical County Emergency Hospital, Targu-Mures, Romania. FAU - Bara, Tivadar Jr AU - Bara T Jr AD - Department of Surgery, Clinical County Emergency Hospital, Targu-Mures, Romania. FAU - Fulop, Zsolt Zoltan AU - Fulop ZZ AD - Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Tirgu-Mures, Romania. AD - Department of Surgery, Clinical County Emergency Hospital, Targu-Mures, Romania. FAU - Gurzu, Simona AU - Gurzu S AUID- ORCID: 0000-0003-3968-5118 AD - Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu-Mures, Romania. AD - Department of Pathology, Clinical County Emergency Hospital, Targu-Mures, Romania. AD - Department of Pathology, Research Center (CCAMF), Tirgu-Mures, Romania. LA - eng PT - Journal Article DEP - 20201020 PL - Egypt TA - J Oncol JT - Journal of oncology JID - 101496537 PMC - PMC7596543 COIS- The authors declare that they have no conflicts of interest. EDAT- 2020/11/05 06:00 MHDA- 2020/11/05 06:01 PMCR- 2020/10/20 CRDT- 2020/11/04 05:42 PHST- 2020/08/27 00:00 [received] PHST- 2020/10/08 00:00 [revised] PHST- 2020/10/12 00:00 [accepted] PHST- 2020/11/04 05:42 [entrez] PHST- 2020/11/05 06:00 [pubmed] PHST- 2020/11/05 06:01 [medline] PHST- 2020/10/20 00:00 [pmc-release] AID - 10.1155/2020/8860174 [doi] PST - epublish SO - J Oncol. 2020 Oct 20;2020:8860174. doi: 10.1155/2020/8860174. eCollection 2020.