MET amplified in NSCLC irrespective of type, genetic background

Jan 20 2015

By Shreeya Nanda, Senior medwireNews Reporter

A third of non-small-cell lung cancers (NSCLCs) show low- to high-level amplification of the MET gene, according to a German study, with no significant difference in frequency across different types of cancer and genetic backgrounds.

Hans-Ulrich Schildhaus, from University Hospital Göttingen, and colleagues explain that alterations in the expression levels of the MET receptor tyrosine kinase, a potential therapeutic target in lung cancer, can be caused by various mechanisms, of which MET gene amplification is one.

Highlighting the “controversial” nature of MET amplification in NSCLC, they used fluorescence in situ hybridisation to assess its prevalence in 693 treatment-naive NSCLC patients, of whom 519 had adenocarcinomas and 174 had squamous cell carcinomas.

Thirty-three percent of the samples included in the study had gains of any level in MET copy number. Of these 22 (3%) tumours had high-level amplification, defined as fulfilling one of the following criteria: MET/centromere 7 ratio of at least 2.0; average MET gene copy number per cell of 6.0 or higher; and/or at least 10% of tumour cells containing 15 or more copies of the MET gene.

A total of 43 (6%) carcinomas had intermediate- and 162 (24%) had low-level gains, defined as tumours with at least 50% of cells containing five or more MET signals and those with at least 40% of cells with four or more MET gene copies, respectively.

Furthermore, MET amplification was observed in adenocarcinomas, including epidermal growth factor receptor-mutated, Kirsten rat sarcoma viral oncogene homologue-mutated and wild-type tumours, as well as in squamous cell carcinomas of the lung. There were no significant differences in the frequency of high-, intermediate- or low- level amplification between the subgroups.

Schildhaus et al used immunohistochemistry in a subset of 65 cases to show a significant correlation between cells with MET protein overexpression and high-level MET amplification, although this relationship was stronger for tumours with a clear positive or negative result compared with those with borderline findings.

The team writes in Clinical Cancer Research that their research is the “currently most comprehensive” dataset on the prevalence of MET amplification in this patient population, and adds that it “may be useful in the context of screening programs for patients in upcoming clinical trials with c-MET inhibitors.”

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