高 MET 基因拷贝数导致非小细胞肺癌患者的生存时间更短。

High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer.

机构信息

Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

J Thorac Oncol. 2010 Mar;5(3):305-13. doi: 10.1097/JTO.0b013e3181ce3d1d.

DOI:10.1097/JTO.0b013e3181ce3d1d

PMID:20107422

Abstract

INTRODUCTION

Activation of MET, either by increased gene copy number (GCN) or mutation, has been detected in various cancers. We investigate the clinicopathologic features of MET gene copy in nonsmall cell lung cancer (NSCLC).

METHODS

Tumor tissues were obtained from 180 resected NSCLCs, including 97 squamous cell carcinomas (SCCs) and 72 adenocarcinomas. No patient received epidermal growth factor receptor (EGFR)-targeted therapy. EGFR and MET GCNs were studied using fluorescence in situ hybridization (FISH) and were estimated according to the University of Colorado Cancer Center (UCCC) criteria. For MET, we also assessed GCNs using the Cappuzzo system.

RESULTS

FISH-positive MET was observed in 16.7% using the UCCC criteria; specifically, amplification was seen in 3.9% and high polysomy in 12.8%. FISH-positive MET status was significantly correlated with FISH-positive EGFR (p = 0.003). In the Cappuzzo system, high MET GCN (mean, >/=5 copies/cell) was found in 6.7% and also associated with FISH-positive EGFR (p = 0.031). MET gene copy status was not associated with gender, smoking history, histology, or stage. However, true MET amplification was more frequent in patients with SCC than in those with adenocarcinoma. FISH-positive MET status predicted worse survival in patients with NSCLC at advanced stages (p = 0.034) and in patients with SCC (p = 0.028). In multivariate analyses, increased MET GCN was significantly associated with shorter survival in patients with SCC, as analyzed using both the UCCC and Cappuzzo criteria (p = 0.019 and 0.008).

CONCLUSIONS

Our results suggest that increased MET GCN would be an independent poor prognostic factor in SCC of the lung.

摘要

简介

MET 的激活，无论是通过基因拷贝数（GCN）的增加还是突变，在各种癌症中都有检测到。我们研究了非小细胞肺癌（NSCLC）中 MET 基因拷贝的临床病理特征。

方法

从 180 例切除的 NSCLC 组织中获得肿瘤组织，包括 97 例鳞状细胞癌（SCC）和 72 例腺癌。没有患者接受表皮生长因子受体（EGFR）靶向治疗。使用荧光原位杂交（FISH）研究 EGFR 和 MET GCN，并根据科罗拉多大学癌症中心（UCCC）标准进行评估。对于 MET，我们还使用 Cappuzzo 系统评估 GCN。

结果

使用 UCCC 标准，观察到 16.7%的 FISH 阳性 MET；具体来说，扩增见于 3.9%，高多倍体见于 12.8%。FISH 阳性 MET 状态与 FISH 阳性 EGFR 显著相关（p = 0.003）。在 Cappuzzo 系统中，高 MET GCN（平均值，>/=5 拷贝/细胞）见于 6.7%，也与 FISH 阳性 EGFR 相关（p = 0.031）。MET 基因拷贝状态与性别、吸烟史、组织学或分期无关。然而，在 SCC 患者中，真正的 MET 扩增比在腺癌患者中更为常见。FISH 阳性 MET 状态预测晚期 NSCLC 患者（p = 0.034）和 SCC 患者（p = 0.028）的生存更差。在多变量分析中，使用 UCCC 和 Cappuzzo 标准，增加的 MET GCN 与 SCC 患者的生存时间显著相关（p = 0.019 和 0.008）。