Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2016; 22(35): 7926-7937
Published online Sep 21, 2016. doi: 10.3748/wjg.v22.i35.7926
HER2 aberrations and heterogeneity in cancers of the digestive system: Implications for pathologists and gastroenterologists
Nicola Fusco, Silvano Bosari
Nicola Fusco, Silvano Bosari, Division of Pathology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy
Nicola Fusco, Silvano Bosari, Department of Pathophysiology and Organ Transplantation, University of Milan, 20122 Milan, Italy
Conflict-of-interest statement: No conflict of interest.
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:
Correspondence to: Silvano Bosari, MD, Professor, Division of Pathology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy.
Telephone: +39-2-55032415 Fax: +39-2-55032415
Received: April 27, 2016
Peer-review started: April 29, 2016
First decision: July 13, 2016
Revised: August 1, 2016
Accepted: August 10, 2016
Article in press: August 10, 2016
Published online: September 21, 2016

Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-of-knowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.

Keywords: HER2, Digestive system, Gastrointestinal tract, Gastric cancer, Colon cancer, Esophageal cancer, Gastroesophageal junction cancer, Biliary tract cancer, Gallbladder cancer, Liver cancer, Pancreas cancer

Core tip: Numerous studies have broadened our understanding of HER2 as a critical oncogene in many human cancers, including tumors of the digestive system. Due to the increasing importance of HER2 testing in this heterogeneous group of tumors, in this review we seek to outline the current state of knowledge of HER2 alterations in the most common malignancies occurring in the digestive system, to examine the operational implications of HER2 testing as a biomarker and potentially targetable gene, and discuss immediate future perspectives for pathologists and gastroenterologists.