MET Expression Level in Lung Adenocarcinoma Loosely Correlates with MET Copy Number Gain/Amplification and Is a Poor Predictor of Patient Outcome

Simple Summary MET is a proto-oncogene and plays an important role on tumor cell survival, proliferation, metastasis, and drug resistance. Patient with MET amplification has shown an inferior outcome comparing to patients without MET amplification. Fluorescence in situ hybridization (FISH) is often used to detect MET amplification, and immunohistochemistry (IHC) is often used to assess MET expression level. Though some institutions provide both tests, IHC is more readily available in most pathology laboratories and is cheaper than FISH. This study evaluated the correlation of MET expression level with MET copy number gain/amplification, and the MET overexpression with patient's outcome. By studying 446 patients with lung adenocarcinoma, we found that the concordance of MET expression and MET copy number gain/amplification was low; high-level of MET expression was associated with inferior outcome, but it was not an independent poor prognostic factor. These findings indicate that IHC for MET expression can't substitute FISH analysis for MET amplification. MET amplification has been associated with shorter survival in cancer patients, however, the potential correlation of MET overexpression with either MET amplification or patient outcome is controversial. The aim of this study was to address these questions by correlating MET expression level with MET copy number and patient outcome in a cohort of 446 patients who had a lung adenocarcinoma: 88 with MET amplification, 118 with polysomy 7, and 240 with negative results by fluorescence in situ hybridization. MET expression assessed by immunohistochemistry was semi-quantified by expression level: absent (0+), weak (1+), moderate (2+) and strong (3+); or by H-score: 0-99, 100-199, and >= 200. MET expression level or H-score was positively but weakly correlated with MET copy number or MET/CEP7 ratio. Strong expression of MET (3+ or H-score >= 200) was associated with a shorter overall survival, but it was not an independent hazard for survival by multivariant analysis. We conclude that MET expression is loosely correlated with MET copy number gain/amplification. Strong expression of MET does not independently predict patient outcome.

Automated summary

This study evaluated the correlation of MET expression level with MET copy number gain/amplification, and the MET overexpression with patient's outcome. The study found that the concordance of MET expression and MET copy number gain/amplification was low; high-level of MET expression was associated with inferior outcome, but it was not an independent poor prognostic factor.