从未接受治疗的肺腺癌和鳞癌的MET扩增状态

GeneDiagnostic, ZytoVision

MET amplification status in therapy-naïve adeno-and squamous cell carcinomas of the lung

Schildhaus HU,Schultheis AM,Rüschoff J,et al.

EXPERIMENTAL DESIGN:

We evaluated the prevalence of increased MET gene copy numbers in693treatment-naïve cancers by FISH,defined clear cutoff criteria,and correlated FISH results to MET IHC.

RESULTS:

Two thirds(67%)of lung cancers do not have gains in MET gene copy numbers,whereas3%show a clear-cut high-level amplification(MET/centromer7ratio≥2.0or average gene copy number per nucleus≥6.0or≥10%of tumor cells containing ≥15MET copies).The remaining cases can be subdivided into intermediate-(6%)and low-level gains(24%). Importantly,MET amplifications occur at equal frequencies in squamous and adenocarcinomas without or with EGFR or KRAS mutations.

CONCLUSION:

MET amplification is not a mutually exclusive genetic event in therapy-naïve non-small cell lung cancer.Our data suggest that it might be useful to determine MET amplification(i)before EGFR inhibitor treatment to identify possible primary resistance to anti-EGFR treatment,and(ii)to select cases that harbor KRAS mutations additionally to MET amplification and,thus,may not benefit from MET inhibition.Furthermore,our study provides comprehensive epidemiologic data for upcoming trials with various MET inhibitors.

从未接受治疗的肺腺癌和鳞癌的MET扩增状态

试验设计：

我们针对693例未接受治疗的恶性肿瘤，用FISH（ZytoVision，德国蔡图微）方法，以明确的分界标准评估MET基因扩增状态，同时将FISH结果与MET IHC结果进行相关性比较。

结果：

2/3（67%）的肺癌患者无MET基因增多，而3%的患者显示出明显扩增（MET/CEN7≥2.0或细胞平均基因拷贝数≥6.0或有≥10%的细胞MET拷贝数≥15个）。其余样本可细分为中度（6%）和低水平增多（24%）。重要的是，MET扩增在无论是否有EGFR或KRAS突变的腺癌和鳞癌中发生频率相同。

结论：

在尚未接受治疗的非小细胞肺癌患者中，MET基因扩增并不是一个相互排斥性的基因改变。我们的数据提示，检测MET基因扩增可以：1）在使用EGFR抑制剂之前，以便预测抗EGFR治疗可能出现的耐受性，2）分捡出既有KRAS突变又有MET 扩增的病例，这种情况下病人可能不能从MET抑制治疗中获益。此外，我们的研究为将来多种MET抑制剂试验提供了综合的流行病学数据。