Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2019; 11(4): 335-347
Published online Apr 15, 2019. doi: 10.4251/wjgo.v11.i4.335
Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas
Xin-Yu Wang, Zhi-Xue Zheng, Yu Sun, Yan-Hua Bai, Yun-Fei Shi, Li-Xin Zhou, Yun-Feng Yao, Ai-Wen Wu, Deng-Feng Cao
Xin-Yu Wang, Yu Sun, Yan-Hua Bai, Yun-Fei Shi, Li-Xin Zhou, Deng-Feng Cao, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing 100142, China
Zhi-Xue Zheng, Yun-Feng Yao, Ai-Wen Wu, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
Zhi-Xue Zheng, Department of General Surgery, Beijing Jishuitan Hospital, Beijing 100035, China
Deng-Feng Cao, Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, United States
Author contributions: Wang XY and Zheng ZX contributed equally to this work; all authors helped to perform the research; Wang XY manuscript writing, performing procedures and data analysis; Zheng ZX contribution to writing the manuscript, drafting conception and design; Wang XY and Zheng ZX contribution to writing the manuscript equally; Sun Y manuscript writing, drafting conception and design, performing experiments, and data analysis; Bai YH, Shi YF, Zhou LX, Yao YF and Wu AW contribution to writing the manuscript; Cao DF contribution to writing the manuscript drafting conception and design.
Supported by Special Scientific Research Key Project for Capital Health Development, China, No. 2018-2Z-1026.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Beijing Cancer Hospital.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
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/
Corresponding author: Yu Sun, MD, PhD, Associate Professor, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China. sunyu_bch@163.com
Telephone: +86-10-88196700 Fax: +86-10-88196700
Received: December 26, 2018
Peer-review started: December 26, 2018
First decision: January 11, 2019
Revised: February 13, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: April 15, 2019
Processing time: 111 Days and 5.8 Hours
ARTICLE HIGHLIGHTS
Research background

The vast majority of colorectal cancers are adenocarcinomas. Until recently, the role of chemotherapy in treating colorectal adenocarcinomas (CRCs) has been fairly limited, and as such there is a need to develop more effective therapeutic regimes for CRC. Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver; it’s a well-established therapeutic target in breast and gastric cancers.

Research motivation

The role of HER2 as a prognostic biomarker in CRCs remains uncertain, but its relevance as a therapeutic target has been established.

Research objectives

In this study, the authors aim to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables.

Research methods

In this study, to assess HER2 protein expression, 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining (IHC). And to assess HER2 gene amplification, 141 selected tumors were further evaluated by fluorescence in situ hybridization (FISH). The authors investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis.

Research results

HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+, 12/102 tumors with an IHC score of 2+, and 0 tumors with IHC score of 1+ (0/10). HER2 gene amplification was seen in 36/1191 tumors. Among the tumors with HER2 IHC scores of 3+ and 2+, the mean percentage of tumor cells with positive IHC staining was 90% and 67%. Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining than those without. HER2 gene status was significantly associated with distant tumor metastasis and stage. HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival (OS) or disease-specific survival for the overall group of 1058 patients. Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores (2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores (0, 1+).

Research conclusions

HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression confers a worse prognosis in patients 65 years old or younger with tubular adenocarcinomas.