Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Clin Lung Cancer. 2021 Jul;22(4):e512-e518. doi: 10.1016/j.cllc.2020.11.002. Epub 2020 Nov 17.
The MET pathway is a promising target in patients with non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization analysis has become a standard method to detect MET amplification. However, no consensus has been reached regarding the definition of MET amplification. We aimed to find clinically meaningful cutoffs for MET amplification that could be used as a prognostic marker and/or indication for MET inhibitor therapy.
We reviewed the fluorescence in situ hybridization results of MET/CEP7 (centromere of chromosome 7) for 2260 patients with treatment-naive NSCLC from 2014 to 2019. Clinical and pathologic data were collected from the medical records. Log-rank tests and Cox proportional hazard models were used to estimate the overall survival (OS) among patients with different MET/CEP7 ratios and/or MET copy numbers.
Of the 2260 patients, 130 (5.8%) had had a MET/CEP7 ratio of ≥ 1.8 and 13 (0.6%) had had a ratio of ≥ 5.0. Of these 130 patients with a MET/CEP7 ratio of ≥ 1.8, 123 (95%) also had a MET copy number of ≥ 5. In general, a higher MET copy number and higher MET/CEP7 ratio were associated with advanced tumor stage. The OS was significantly shorter when the MET copy number was ≥ 10 and/or when the MET/CEP7 ratio was ≥ 1.8. A MET/CEP7 ratio of ≥ 1.8 remained a significant hazard to OS on multivariate analysis (hazard ratio, 1.63; P = .019).
Patients with a MET copy number of ≥ 10 and/or MET/CEP7 ratio of ≥ 1.8 showed significantly poorer survival, and a MET/CEP7 ratio of ≥ 1.8 was an independent poor prognostic factor.
MET 通路是治疗非小细胞肺癌（NSCLC）患者的一个有前景的靶点。荧光原位杂交分析已成为检测 MET 扩增的标准方法。然而，对于 MET 扩增的定义尚未达成共识。我们旨在寻找具有临床意义的 MET 扩增截断值，这些截断值可用作预后标志物和/或 MET 抑制剂治疗的指征。
我们回顾了 2014 年至 2019 年间 2260 例未经治疗的 NSCLC 患者的 MET/CEP7（染色体 7 着丝粒）荧光原位杂交结果。从病历中收集临床和病理数据。采用对数秩检验和 Cox 比例风险模型估计不同 MET/CEP7 比值和/或 MET 拷贝数患者的总生存期（OS）。
在 2260 例患者中，有 130 例（5.8%）的 MET/CEP7 比值≥1.8，有 13 例（0.6%）的比值≥5.0。在这 130 例 MET/CEP7 比值≥1.8 的患者中，有 123 例（95%）的 MET 拷贝数≥5.0。一般来说，较高的 MET 拷贝数和较高的 MET/CEP7 比值与晚期肿瘤分期相关。当 MET 拷贝数≥10 且/或 MET/CEP7 比值≥1.8 时，OS 显著缩短。多因素分析显示，MET/CEP7 比值≥1.8 仍然是 OS 的显著危险因素（风险比，1.63；P=0.019）。
MET 拷贝数≥10 和/或 MET/CEP7 比值≥1.8 的患者的生存明显较差，MET/CEP7 比值≥1.8 是独立的不良预后因素。
