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胃癌中 HER2 基因扩增与化疗敏感性联合检测的方法及意义。

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

机构信息

Department of Pathology, Shenzhen Baoan Hospital of Traditional Chinese Medicine (Group), Shenzhen 518133, Guangdong, China.

Shenzhen Polytechnic, School of Electronic and Communication Engineering, Shenzhen 518055, Guangdong, China.

出版信息

Cancer Biomark. 2018 Feb 6;21(2):439-447. doi: 10.3233/CBM-170671.

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.

摘要

目的

本研究旨在探讨联合检测胃癌中 HER2 基因扩增和化疗敏感性的意义。

方法

采用免疫组织化学(IHC)、荧光原位杂交(FISH)和荧光逆转录聚合酶链反应(RT-PCR)分析 135 例胃癌中 HER2 蛋白表达、HER2 基因扩增以及 ERCC1、TUBB3 和 TYMS 基因的 mRNA 表达。

结果

HER2 蛋白表达阳性率为 39.3%(53/135)。其中 HER2 蛋白(3+)患者占 9.6%(13/135),HER2 蛋白(2+)患者占 13.3%(18/135),HER2 蛋白(1+)患者占 16.3%(22/135)。HER2 基因扩增率为 35.8%(19/53)。在检测 ERCC1、TUBB3 和 TYMS 的 mRNA 表达时,45 例患者存在低中强度单基因表达,50 例患者存在低中强度双基因表达,22 例患者存在 ERCC1、TUBB3 和 TYMS 低中强度 mRNA 表达,18 例患者无低中强度表达。在 53 例 HER2 蛋白表达阳性和 22 例 ERCC1、TUBB3 和 TYMS 低中强度 mRNA 表达的患者中,12 例患者接受化疗和曲妥珠单抗治疗。随访结果显示,HER2 基因状态与低 mRNA 表达的 ERCC1、TUBB3 和 TYMS 患者联合治疗的疗效呈正相关。在这些患者中,5 例广泛 HER2(3+)、HER2 簇特异性扩增、低 mRNA 表达的 ERCC1、TUBB3 和 TYMS 的患者总生存期长达 19.1 个月。

结论

胃癌中 HER2 的检测具有高度异质性,联合检测 HER2 蛋白表达、HER2 基因扩增和化疗敏感性可为抗肿瘤药物的获益提供重要参考标志物。

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