title: HER2 heterogeneity in gastric/gastroesophageal cancers: From benchside to practice.
abstract: HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit from targeted therapies with anti-HER2 drugs such as Trastuzumab. This manuscript focuses on HER2 in gastric carcinogenesis, on optimal evaluation of HER2 and on the possible causes which may contribute to inaccurate HER2 evaluation. Similarly to breast cancer HER2 evaluation, standardization of HER2 testing in gastric cancer is necessary in diagnostic practice. The three principle aspects which require consideration are: (1) the choice of sample with regards to cancer morphology - intestinal vs diffuse areas; (2) the choice of scoring criteria - use of HER2 scoring criteria specific for gastric cancer; and (3) the choice of HER2 evaluation methods - use of an algorithm in which both immunohistochemistry and in situ hybridization play a role. Problematic issues include: (1) pre-analytic variables with particular emphasis on fixation; (2) recommended methodology for HER2 assessment (immunohistochemistry vs in situ hybridization); (3) HER2 heterogeneity both within the primary tumor and between primary tumor and metastases; (4) reliability of biopsies in HER 2 evaluation; and (5) quantity of sample (FFPE blocks from surgical specimens or endoscopic biopsies) necessary for an adequate assessment.
authors.affiliation: Federica Grillo, Francesca Sarocchi, Roberto Fiocca, Luca Mastracci, Department of Surgical and Diagnostic Sciences, Pathology Unit, University of Genoa, 16132 Genoa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Grillo
authors.affiliation: Federica Grillo, Francesca Sarocchi, Roberto Fiocca, Luca Mastracci, Department of Surgical and Diagnostic Sciences, Pathology Unit, University of Genoa, 16132 Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Federica Grillo, Francesca Sarocchi, Roberto Fiocca, Luca Mastracci, Department of Surgical and Diagnostic Sciences, Pathology Unit, University of Genoa, 16132 Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sarocchi
authors.affiliation: Federica Grillo, Francesca Sarocchi, Roberto Fiocca, Luca Mastracci, Department of Surgical and Diagnostic Sciences, Pathology Unit, University of Genoa, 16132 Genoa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fiocca
authors.affiliation: Federica Grillo, Francesca Sarocchi, Roberto Fiocca, Luca Mastracci, Department of Surgical and Diagnostic Sciences, Pathology Unit, University of Genoa, 16132 Genoa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Mastracci
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D063646:Carcinogenesis; D004943:Esophagogastric Junction; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D018579:Patient Selection; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: FISH; Gastric cancer; HER2; Heterogeneity; Immunohistochemistry