三种不同方法检测结直肠癌 EGFR、HER2、c-MYC 和 MET 变异的对比分析：基因拷贝数增益、扩增状态和 2013 年 ASCO/CAP 乳腺癌 HER2 检测指南标准。

Comparative analysis of the EGFR, HER2, c-MYC, and MET variations in colorectal cancer determined by three different measures: gene copy number gain, amplification status and the 2013 ASCO/CAP guideline criterion for HER2 testing of breast cancer.

机构信息

Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, Republic of Korea.

Department of Diagnostic Pathology, Samkwang Medical Laboratories, Seoul, Republic of Korea.

出版信息

J Transl Med. 2017 Aug 1;15(1):167. doi: 10.1186/s12967-017-1265-x.

DOI:10.1186/s12967-017-1265-x

PMID:28764718

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5540452/

Abstract

BACKGROUND

The purpose of this study was to explore gene copy number (GCN) variation of EGFR, HER2, c-MYC, and MET in patients with primary colorectal cancer (CRC).

METHODS

Dual-colour silver-enhanced in situ hybridization was performed in tissue samples of 334 primary CRC patients. The amplification status (GCN ratio ≥2) and GCN gain (average GCN ≥4) data for the EGFR, HER2, c-MYC and MET genes were obtained. GCN variation was also assessed by the criterion of the 2013 ASCO/CAP guidelines for HER2 testing.

RESULTS

Amplification of EGFR, HER2, c-MYC and MET was detected in 8 (2.4%), 20 (6.0%), 29 (8.7%), and 14 (4.2%) patients, respectively. Of 66 patients with at least one amplified gene, five exhibited co-amplification of genes studied (HER2-MET co-amplification: two patients; HER2-c-MYC co-amplification: two patients; EGFR-c-MYC co-amplification: one patient). There were 109 patients with GCN gains of one or more genes (EGFR: 11/334, HER2: 29/334, c-MYC; 60/334, MET: 48/334) and 32.1% (35/109) had multiple GCN gains. When each GCN was assessed by the criterion of the ASCO/CAP 2013 guideline for HER2 testing, 116 people showed positive or equivocal results for one or more genes. The cumulative amplification status had no association with patients' outcome. However, the cumulative results of the GCN gain and GCN status determined according to the ASCO/CAP guideline had a significant prognostic correlation in the univariate analysis (P values of 0.006 and 0.022, respectively). In the multivariate analysis, GCN gain and GCN status were independent prognostic factors (P values of 0.010 and 0.017, respectively).

CONCLUSIONS

In this study, we evaluated GCN variation of four genes in a large sample of Korean CRC patients. The amplification status was not related to patient outcome. However, the GCN gain and GCN status according to the ASCO/CAP 2013 guideline were independent prognostic factors.

摘要

背景

本研究旨在探讨原发性结直肠癌（CRC）患者中 EGFR、HER2、c-MYC 和 MET 基因的拷贝数（GCN）变异。

方法

对 334 例原发性 CRC 患者的组织样本进行双色银增强原位杂交。获得 EGFR、HER2、c-MYC 和 MET 基因的扩增状态（GCN 比值≥2）和 GCN 增益（平均 GCN≥4）数据。根据 2013 年 ASCO/CAP 检测 HER2 指南的标准，还评估了 GCN 变异。

结果

分别在 8 例（2.4%）、20 例（6.0%）、29 例（8.7%）和 14 例（4.2%）患者中检测到 EGFR、HER2、c-MYC 和 MET 扩增。在 66 例至少有一种扩增基因的患者中，有 5 例表现为研究基因的共扩增（HER2-MET 共扩增：2 例；HER2-c-MYC 共扩增：2 例；EGFR-c-MYC 共扩增：1 例）。有 109 例患者出现一种或多种基因的 GCN 增益（EGFR：11/334；HER2：29/334；c-MYC：60/334；MET：48/334），32.1%（35/109）患者有多种 GCN 增益。当根据 ASCO/CAP 2013 年 HER2 检测指南的标准评估每个 GCN 时，有 116 人显示一种或多种基因的阳性或不确定结果。累积扩增状态与患者的预后无关。然而，根据 ASCO/CAP 指南确定的 GCN 增益和 GCN 状态的累积结果在单因素分析中具有显著的预后相关性（P 值分别为 0.006 和 0.022）。在多因素分析中，GCN 增益和 GCN 状态是独立的预后因素（P 值分别为 0.010 和 0.017）。