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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2016; 22(26): 5879-5887
Published online Jul 14, 2016. doi: 10.3748/wjg.v22.i26.5879
HER2 heterogeneity in gastric/gastroesophageal cancers: From benchside to practice
Federica Grillo, Matteo Fassan, Francesca Sarocchi, Roberto Fiocca, Luca Mastracci
Federica Grillo, Francesca Sarocchi, Roberto Fiocca, Luca Mastracci, Department of Surgical and Diagnostic Sciences, Pathology Unit, University of Genoa, 16132 Genoa, Italy
Federica Grillo, Roberto Fiocca, Luca Mastracci, Institute for Research and Cure of Cancer (IRCCS) S. Martino-IST University Hospital, 16132 Genoa, Italy
Matteo Fassan, Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, 35121 Padua, Italy
Author contributions: Grillo F, Sarocchi F and Mastracci L wrote the paper; Fassan M and Fiocca R critically reviewed the paper.
Conflict-of-interest statement: All authors declare no conflicting interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Luca Mastracci, Assistant Professor of Pathology, Department of Surgical and Diagnostic Sciences, Pathology Unit, University of Genoa and IRCCS S. Martino-IST University Hospital, 16132 Genoa, Italy. mastracc@hotmail.com
Telephone: +39-10-5555954 Fax: +39-10-5556605
Received: March 24, 2016
Peer-review started: March 24, 2016
First decision: May 12, 2016
Revised: May 13, 2016
Accepted: May 21, 2016
Article in press: May 23, 2016
Published online: July 14, 2016
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.

Keywords: Gastric cancer, HER2, Heterogeneity, Immunohistochemistry, FISH

Core tip: Accurate assessment of HER2 status is mandatory in gastric/gastroesophageal cancer, for selecting patients who may benefit from targeted therapies with anti-HER2 drugs. The three principle aspects of HER2 evaluation which require consideration are: (1) choice of sample with regards to cancer morphology; (2) choice of scoring criteria; and (3) choice of HER2 evaluation methods. Problematic issues include: (1) pre-analytic variables; (2) recommended methodology for HER2 assessment; (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 necessary for adequate assessment.