HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer

doi:10.12998/wjcc.v7.i15.1964

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 7, Issue 15

This Article

Peer-Review Report of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (11031)

All Articles published online

The chart showing PDF series, WORD series, HTML series, Figures (1-5) series, Tables (1-2) series.

Item

Count

PDF

709

WORD

327

HTML

5223

Figures (1-5)

772

Tables (1-2)

618

Sum=7649

Publishing Process of This Article

The chart showing Browse series, Download series.

Item

Count

Browse

1306

Download

2061

Sum=3367

Aug 6, 2019 (publication date) through Feb 22, 2026

Times Cited of This Article

Times Cited (53)

Journal Information of This Article

Publication Name

World Journal of Clinical Cases

ISSN

2307-8960

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

- Full Article with Cover (PDF)
- Full Article (XML)

Retrospective Study

World J Clin Cases. Aug 6, 2019; 7(15): 1964-1977
Published online Aug 6, 2019. doi: 10.12998/wjcc.v7.i15.1964

HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer

Akio Kaito, Takeshi Kuwata, Masanori Tokunaga, Kohei Shitara, Reo Sato, Tetsuo Akimoto, Takahiro Kinoshita

Akio Kaito, Masanori Tokunaga, Reo Sato, Takahiro Kinoshita, Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa 277-8577, Japan

Akio Kaito, Takeshi Kuwata, Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa 277-8577, Japan

Akio Kaito, Kohei Shitara, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, Japan

Takeshi Kuwata, Kohei Shitara, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center Hospital East, Kashiwa 277-8577, Japan

Tetsuo Akimoto, Juntendo University Graduate School of Medicine, Tokyo 163-8001, Japan

Tetsuo Akimoto, Department of Radiation Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, Japan

Author contributions: Kaito A and Kuwata T contributed equally to this work in study conception, study design, data acquisition, quality control of data and algorithms, and data analysis and interpretation; Kaito A contributed to statistical analysis and manuscript preparation; All authors contributed equally to manuscript editing and manuscript review.

Institutional review board statement: This study was approved by the Institutional Review Board of the National Cancer Center, Japan, No. 2017-164, approval date: Oct. 11, 2017.

Informed consent statement: Comprehensive informed consent including publication without personally identifiable information was obtained from all of the subjects prior to study enrollment. Thus, specified informed consent for this study is not required. The public document of this study was published on our website: https://www.ncc.go.jp/jp/about/research_promotion/study/list/2017-164.pdf. Informed consent statement could not be obtained because most of the participants were deceased.

Conflict-of-interest statement: The authors have no conflict of interest to declare.

Corresponding author: Takeshi Kuwata, MD, PhD, Doctor, Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa 277-8577, Japan. tkuwata@east.ncc.go.jp

Telephone: +81-4-71331111 Fax: +81-4-71300190

Received: April 13, 2019
Peer-review started: April 15, 2019
First decision: May 16, 2019
Revised: June 16, 2019
Accepted: June 26, 2019
Article in press: June 27, 2019
Published online: August 6, 2019
Processing time: 115 Days and 8.2 Hours

Abstract

BACKGROUND

The clinical significance of intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity is unclear for HER2-positive gastric cancer, although it has been reported to be a significant prognosticator for HER2-positive breast cancer, which has received trastuzumab-based chemotherapy.

AIM

To clarify the clinical significance of intratumoral HER2 heterogeneity for HER2-positive gastric cancer, which has received trastuzumab-based chemotherapy.

METHODS

Patients with HER2-positive unresectable or metastatic gastric cancer who received trastuzumab-based chemotherapy as a first line treatment were included. The patients were classified into two groups according to their intratumoral HER2 heterogeneity status examined by immunohistochemistry (IHC) on endoscopic biopsy specimens before treatment, and their clinical response to chemotherapy and survival were compared.

RESULTS

A total of 88 patients were included in this study, and HER2 heterogeneity was observed in 23 (26%) patients (Hetero group). The overall response rate was significantly better in patients without HER2 heterogeneity (Homo group) (Homo vs Hetero: 79.5% vs 35.7%, P = 0.002). Progression-free survival of trastuzumab-based chemotherapy was significantly better in the Homo group (median, 7.9 vs 2.5 mo, HR: 1.905, 95%CI: 1.109-3.268). Overall survival was also significantly better in the Homo group (median survival time, 25.7 vs 12.5 mo, HR: 2.430, 95%CI: 1.389-4.273). Multivariate analysis revealed IHC HER2 heterogeneity as one of the independent poor prognostic factors (HR: 3.115, 95%CI: 1.610-6.024).

CONCLUSION

IHC of HER2 heterogeneity is the pivotal predictor for trastuzumab-based chemotherapy. Thus, HER2 heterogeneity should be considered during the assessment of HER2 expression.

Keywords: Human epidermal growth factor receptor 2; Heterogeneity; Trastuzumab; Gastric cancer; Chemotherapy

Core tip: Although intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity has been reported as an important predictor of trastuzumab-based chemotherapy for HER2-positive breast cancer, the clinical significance of HER2 heterogeneity for gastric cancer had been unclear. We defined intratumoral HER2 heterogeneity as biopsy specimens were taken from two or more different portions of the tumor that showed different HER2 positivity by immunohistochemistry, and HER2 heterogeneity based on this definition was a pivotal poor predictor of tumor shrinkage and poor prognosticator. Thus, intratumoral HER2 heterogeneity should be included in the assessment of HER2 positivity.