Human epidermal growth factor receptor 2 expression in mixed gastric carcinoma

doi:10.3748/wjg.v21.i15.4680

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Apr 21, 2015; 21(15): 4680-4687
Published online Apr 21, 2015. doi: 10.3748/wjg.v21.i15.4680

Human epidermal growth factor receptor 2 expression in mixed gastric carcinoma

Yang-Kun Wang, Zhong Chen, Tian Yun, Cong-Yang Li, Bo Jiang, Xue-Xia Lv, Guang-Hui Chu, Su-Nan Wang, Hui Yan, Lei-Feng Shi

Yang-Kun Wang, Tian Yun, Xue-Xia Lv, Department of Pathology, 150^th Luoyang Center Hospital, Luoyang 471031, Henan Province, China

Zhong Chen, Department of Medicine Genetic, University of Utah School of Medicine, UT 84095, United States

Cong-Yang Li, Department of Pathology, 152^nd Center Hospital, Pingdingshan 467000, Henan Province, China

Bo Jiang, Department of Pathology, 159^th Center Hospital, Zhumadian 453000, Henan Province, China

Guang-Hui Chu, Hui Yan, Lei-Feng Shi, Department of Gastrointestinal Surgery, 150^th Luoyang Center Hospital, Luoyang 471031, Henan Province, China

Su-Nan Wang, Institute of Computer Technology, School of Electronics and Communication Engineering, Shenzhen 518055, Guangdong Province, China

Author contributions: Wang YK and Shi LF contributed equally to this article; Wang YK and Shi LF designed the project and wrote the manuscript; Li CY, Jiang B and Lv XX conducted data analysis and literature review; Yun T, Chu GH and Wang SN performed immunohistochemistry and fluorescence in situ hybridization analyses; Chen Z and Yan H provided clinical information; all authors have read and approved the final manuscript.

Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.

Conflict-of-interest: There are no conflicts of interest to report.

Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at Shilf_150@163.com.

Correspondence to: Lei-Feng Shi, Professor, Department of Gastrointestinal Surgery, 150^th Luoyang Center Hospital, HuaXia West Road No. 2, Gaoxin District, Luoyang 471031, Henan Province, China. shilf_150@163.com

Telephone: +86-379-64169432 Fax: +86-379-641869564

Received: November 20, 2014
Peer-review started: November 21, 2014
First decision: December 11, 2014
Revised: December 29, 2014
Accepted: February 11, 2015
Article in press: February 11, 2015
Published online: April 21, 2015
Processing time: 151 Days and 3.8 Hours

Abstract

AIM: To investigate human epidermal growth factor receptor 2 (HER2) amplification and protein expression in mixed gastric carcinoma.

METHODS: Fluorescence in situ hybridization and immunohistochemistry were used to detect HER2 amplification and protein expression in 277 cases of mixed gastric carcinoma. Protein staining intensity was rate as 1+, 2+, or 3+.

RESULTS: Of the 277 cases, 114 (41.2%) expressed HER2 protein. HER2 3+ staining was observed in 28/277 (10.1%) cases, 2+ in 37/277 (13.4%) cases, and 1+ in 49/277 (17.7%) cases. A HER2 amplification rate of 17% was detected, of which 25/28 (89.3%) were observed in the HER2 3+ staining group, 17/37 (45.9%) in 2+, and 5/49 (10.2%) in 1+. Of the 47 patients with HER2 amplification who received chemotherapy plus trastuzumab, 22 demonstrated median progression-free and overall survivals of 9.1 mo and 16.7 mo, respectively, which were significantly better than those achieved with chemotherapy alone (5.6 mo and 12.1 mo, respectively) in 19 previously treated patients (Ps < 0.05).

CONCLUSION: HER2 detection in mixed gastric carcinoma displays high heterogeneity. Relatively quantitative parameters are needed for assessing the level of HER2 amplification and protein expression.

Keywords: Fluorescence in situ hybridization; Gastric pathology; Human epidermal growth factor receptor 2; Immunohistochemistry; Stomach

Core tip: Human epidermal growth factor receptor 2 (HER2) detection in mixed gastric carcinoma displays high heterogeneity; a standard detection of HER2 in mixed gastric cancer is needed to better guide therapeutic interventions. In this study, immunohistochemistry and fluorescence in situ hybridization were used to detect HER2 protein expression and amplification, respectively. HER2 staining was classified as extensive, partial, and focal, whereas amplification patterns were classified into cluster, large granule, dot, and HH-17 categories. Clinical therapeutic findings from the patients validated these approaches for assessing the levels of HER2, and demonstrate their clinical applicability.