Methods and significance of the combined detection of HER2 gene amplification and chemosensitivity in gastric cancer

Article type: Research Article

Authors: Wang, Yang-Kun^a | Wang, Su-Nan^b | Li, Ying-Ying^b | Wang, Gong-Ping^c | Yun, Tian^d | Zhu, Chao-Ya^d | Yang, Bin-Feng^d | Li, Cong-Yang^e | Jiang, Bo^e | Zhu, Mei-Ling^{a; *}

Affiliations: [a] Department of Pathology, Shenzhen Baoan Hospital of Traditional Chinese Medicine (Group), Shenzhen 518133, Guangdong, China | [b] Shenzhen Polytechnic, School of Electronic and Communication Engineering, Shenzhen 518055, Guangdong, China | [c] Department of Gastrointestinal Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, Henan, China | [d] Department of Pathology, 150 Hospital of Luoyang, Luoyang 471031, Henan, China | [e] Department of Pathology, The 152 Hospital of Pingdingshan, Pingdingshan 467000, Henan, China

Correspondence: [*] Corresponding author: Mei-Ling Zhu, Department of Pathology, The 152 Hospital of Pingdingshan, Pingdingshan 467000, Henan, China. Tel.: +86 0755 27888933; Fax: +86 0755 2780 2542; E-mail: [email protected].

Abstract: OBJECTIVE: This study aims to investigate the significance of combined detection of HER2 gene amplification and chemosensitivity in gastric cancer. METHODS: Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and fluorescence reverse-transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of HER2 protein, HER2 gene amplification and the mRNA expression of ERCC1, TUBB3 and TYMS genes in 135 cases of gastric carcinoma. RESULTS: The expression rate of HER2 protein was 39.3% (53/135). Among these positive cases, patients with HER2 protein (3+) accounted for 9.6% (13/135), patients with HER2 protein (2+) accounted for 13.3% (18/135), and patients with HER2 protein (1+) accounted for 16.3% (22/135). The amplification rate of the HER2 gene was 35.8% (19/53). In the detection of the mRNA expression of ERCC1, TUBB3 and TYMS, 45 patients had low and moderate single gene expression, 50 patients had low and moderate double gene expression, 22 patients had low and moderate mRNA expression for ERCC1, TUBB3 and TYMS, and 18 patients had no low and moderate expression. Among the 53 patients with HER2 protein expression and 22 patients with low and moderate mRNA expression of ERCC1, TUBB3 and TYMS, 12 patients received chemotherapy and trastuzumab. Follow-up results revealed that HER2 gene status was positively correlated with the therapeutic effect of the combined treatment in patients with low mRNA expression of ERCC1, TUBB3 and TYMS. Among these patients, five patients with extensive HER2 (3+), HER2 cluster-specific amplification, and low mRNA expression of ERCC1, TUBB3 and TYMS had a total survival of up to 19.1 months. CONCLUSIONS: The detection of HER2 in gastric cancer is highly heterogeneity, and the combined detection of HER2 protein expression, HER2 gene amplification and chemosensitivity can provide important reference markers for the benefit of antitumor drugs.

Keywords: Stomach neoplasms, HER2 gene, HER2 protein, FISH, IHC, fluorescence RT-PCR

DOI: 10.3233/CBM-170671

Journal: Cancer Biomarkers, vol. 21, no. 2, pp. 439-447, 2018