Predictive and prognostic value of de novo MET expression in patients with advanced non-small-cell lung cancer

Lung Cancer. 2015 Dec;90(3):375-80. doi: 10.1016/j.lungcan.2015.10.021. Epub 2015 Nov 8.

Abstract

Background: Cellular-mesenchymal-epithelial transition (MET) protein has recently been identified as a novel target that shows promise for the treatment of non-small-cell lung cancer (NSCLC). However, the relationship between de novo MET expression and patient outcomes remains unclear.

Methods: We reviewed the data of patients who had been diagnosed with NSCLC between December 2013 and October 2014. All the patients were evaluated for MET expression status. MET-positive was defined as having an H-score ≥ 60 by immunohistochemistry analysis. MET expression was analyzed in 158 patients who were negative for the common driver genes, including EGFR, ALK, KRAS and ROS1. A chi-squared test was used to assess the clinicopathological parameters. Multivariate analyses were performed using the Cox proportional hazards model.

Results: MET data were available for analysis in 158 advanced NSCLC patients. Of these, based on the MET H-score criteria, the IHC-positive rate was 48.1% (76/158). There were more patients with adenocarcinoma in the MET-positive group compared with the MET-negative group (P=0.01). Nine patients with lymphoepithelioma-like carcinoma had no MET expression. There was no significant difference in overall survival (OS) between MET-positive and -negative patients. There was also no significant difference in the efficacy (Z=-0.44, P=0.66) or progression free survival (PFS) of first-line chemotherapy between the MET-positive and -negative patients (mPFS 6.8 months [95% CI: 5.4-8.2] vs. 5.9 months [5.5-6.3], P=0.92). In the cell model, the MET-positive cell showed no difference in chemotherapy but with a increase in percentage of growth inhibition upon treatment with MET inhibitor INC280 compared to MET-negative cell.

Conclusion: Our data showed that de novo MET expression was not rare. It was not a predictive or prognostic factor for stage IV NSCLC patients, but this should be confirmed in larger population cohort.

Keywords: Chemotherapy; MET; Non-small-cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Cell Line, Tumor
  • Cell Survival
  • Female
  • Gene Expression*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Risk Factors
  • Treatment Outcome

Substances

  • MET protein, human
  • Proto-Oncogene Proteins c-met