Prospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2022; 14(10): 2048-2060
Published online Oct 15, 2022. doi: 10.4251/wjgo.v14.i10.2048
Long-term follow-up of HER2 overexpression in patients with rectal cancer after preoperative radiotherapy: A prospective cohort study
Nan Chen, Chang-Long Li, Yi-Fan Peng, Yun-Feng Yao
Nan Chen, Chang-Long Li, Yi-Fan Peng, Yun-Feng Yao, Department of Gastrointestinal Surgery, Ward III, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
Author contributions: Chen N and Li CL contributed equally to this paper; Chen N and Li CL drafted the manuscript; Chen N, Peng YF and Yao YF designed this study.
Supported by Beijing Municipal Administration of Hospitals Incubating Program, No. PZ2020027; and Beijing Talent Incubating Funding, No. 2019-4.
Institutional review board statement: The study was reviewed and approved by the Beijing Cancer Hospital Institutional Review Board (approval No. 2015KT33).
Clinical trial registration statement: This study is registered at Clinical trial registry of Beijing Cancer Hospital. The registration identification number is 2015KT33.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nan Chen, MD, PhD, Associate Professor, Department of Gastrointestinal Surgery, Ward III, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, No. 52 Fucheng Road, Haidian District, Beijing 100142, China. chennanpku@126.com
Received: March 1, 2022
Peer-review started: March 1, 2022
First decision: April 19, 2022
Revised: May 17, 2022
Accepted: August 24, 2022
Article in press: August 24, 2022
Published online: October 15, 2022
Abstract
BACKGROUND

The role of HER2 overexpression in rectal cancer is controversial.

AIM

To assess the role of HER2 overexpression in the long-term prognosis of rectal cancer.

METHODS

Data from patients with locally advanced rectal cancer who underwent total mesorectal excision after short-course radiotherapy at Beijing Cancer Hospital between May 2002 and October 2005 were collected. A total of 151 tissue samples of rectal cancer were obtained using rigid proctoscopy before neoadjuvant radiotherapy, followed by immunohistochemistry and fluorescence in situ hybridisation to determine the patients’ HER2 expression status. Univariate and multivariate analyses of the associations between the clinicopathological factors and HER2 status were performed. Survival was estimated and compared using the Kaplan-Meier method based on HER2 expression status, and the differences between groups were verified using the log-rank test.

RESULTS

A total of 151 patients were enrolled in this study. A total of 27 (17.9%) patients were ultimately confirmed to be HER2-positive. The follow-up duration ranged from 9 mo to 210 mo, with a median of 134 mo. Distant metastasis and local recurrence occurred in 60 (39.7%) and 24 (15.9%) patients, respectively. HER2 positivity was significantly associated with the pre-treatment lymph node stage (pre-N) (P = 0.040), while there were no differences between HER2 status and age, sex, preoperative CEA levels (pre-CEA), T stage, and lympho-vascular invasion. In terms of prognosis, HER2 overexpression was correlated with distant metastasis (P = 0.002) rather than local recurrence (P > 0.05). The multivariate analysis demonstrated that elevated pre-CEA [P = 0.002, odds ratio (OR) = 3.277, 97.5% confidence interval (CI): 1.543-7.163], post N(+) (P = 0.022, OR = 2.437, 97.5%CI: 1.143-5.308) and HER2(+) (P = 0.003, OR = 4.222, 97.5%CI: 1.667-11.409) were risk factors for distant metastasis. The survival analysis showed that there were significant differences between rectal cancer patients in terms of disease-free survival (DFS) [hazard ratio: 1.69 (95%CI: 0.91-3.14); P = 0.048] and overall survival (OS) [1.95 (1.05-3.63); P = 0.0077].

CONCLUSION

HER2 overexpression is a potential biomarker for predicting lymph node metastasis and distant metastasis, which are associated with worse long-term DFS and OS in rectal cancer patients with locally advanced disease.

Keywords: HER2, Rectal cancer, Distant metastasis, Local recurrence, Survival

Core Tip: Long-term follow-up of rectal cancer patients treated with neoadjuvant radiotherapy demonstrated that pre-treatment HER2 overexpression was significantly correlated with lymph node metastasis and long-term distant metastasis. Furthermore, HER2 overexpression, elevated CEA and lymph node positivity were independent risk factors, predictive for poorer survival.