AUTHOR=Ni Shujuan , Wang Xin , Chang Jinjia , Sun Hui , Weng Weiwei , Wang Xu , Tan Cong , Zhang Meng , Wang Lei , Huang Zhaohui , Huang Dan , Xu Midie , Sheng Weiqi 

TITLE=Human Epidermal Growth Factor Receptor 2 Overexpression and Amplification in Patients With Colorectal Cancer: A Large-Scale Retrospective Study in Chinese Population

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.842787

DOI=10.3389/fonc.2022.842787

ISSN=2234-943X

ABSTRACT=Background Cumulative evidences in colorectal cancer (CRC) suggest that patients with human epidermal growth factor receptor 2 (HER2) overexpression or amplification can benefit from anti-HER2 therapy. The purpose of our study was to evaluate HER2 status and its correlation with clinicopathological characteristics and survival according to currently utilized HER2 diagnostic criteria in a large cohort of Chinese CRC patients.
Methods HER2 protein expression was tested by IHC in formalin-fixed, paraffin-embedded (FFPE) samples from 4836 CRC patients in our institution. Breast cancer (BC) and gastroesophageal adenocarcinoma (GEA) criteria, as well as the HERACLES criteria were used for determination of HER2 status, respectively. Dual color silver-enhanced in situ hybridization (DSISH) was performed in all IHC 2+～3+ cases determined by BC and GEA criteria.
Results The HER2 expression rate of IHC (1+~3+) was 7.01% (339/4836) and 6.02% (291/4836) in CRCs based on the BC/GEA criteria and the HERACLES criteria, respectively; while combined DSISH results the HER2 amplification/overexpression ratio was 3.39% (164/4836) in our cohort. HER2 expression detected by IHC was positively correlated with female gender, whereas the HER2 overexpression/amplification showed no correlation with any clinicopathological parameter. In addition, no significant correlation was found between HER2 statuses and either disease free survival or overall survival regardless of the evaluation criterion was used. However, patients with HER2 1+ CRC showed a tendency of shortest overall survival compared with any other group of patients in according to the HERACLES criteria, and this trend has always existed in the rectal location, T3 stage, and TNM stage II, medium differentiation, and perineural invasion stratified group. Furthermore, the HER2 protein expression was significantly negative correlated with RAS/BRAF mutations according to the HERACLES criteria.
Conclusion To our knowledge, this is the largest study of HER2 status in Asian patients with CRC. Our findings suggest that the current most common used HERACLES criteria might be too strict for patients with CRC. Future studies are needed to explore the most suitable criteria for screening CRC patients who could benefit from anti-HER2 therapy as much as possible.