Skip Navigation LinksHome > May 2014 - Volume 9 - Issue 5 > High MET Receptor Expression But Not Gene Amplification in A...
Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000145
Original Articles

High MET Receptor Expression But Not Gene Amplification in ALK 2p23 Rearrangement Positive Non–Small-Cell Lung Cancer

Feng, Yan MD*†‡; Minca, Eugen C. MD§‖; Lanigan, Christopher MS§; Liu, Angen MD, PhD‡‖; Zhang, Wei MS; Yin, Lihong PhD; Pennell, Nathan A. MD, PhD*‡; Farver, Carol MD; Tubbs, Raymond DO§; Ma, Patrick C. MD, MSc*†‡

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Abstract

Introduction:

Overexpression of MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) and MET gene amplification have been well-documented in non–small-cell lung cancer (NSCLC). Activated MET signaling plays an important role in human cancer tumorigenesis, metastasis, and drug resistance. However, the deregulation of MET/HGF pathway in NSCLC harboring ALK gene rearrangement (ALK[+]), which is sensitive to dual ALK and MET inhibitor Crizotinib, has not been reported.

Methods:

We performed systematic analysis of MET/HGF expression by immunohistochemistry (IHC) and MET gene amplification by dual color, dual hapten bright field in situ hybridization in 19 ALK(+) and 73 ALK(−) NSCLC tumor tissues from those who had clinical ALK rearrangement test done at the Cleveland Clinic from August 2010 to January 2013. IHC scoring was interpreted on a standard four-tier system.

Results:

The percentage of MET IHC score 0, 1+, 2+, and 3+ were 5.5%, 27.8%, 50.0%, and 16.7% in ALK(+) group, compared with 28.8%, 33.9%, 23.7%, and 13.6% in ALK(−) group, respectively. The MET high expression (IHC score 2 or 3) was significantly higher in ALK(+) group statistically (66.7% versus 37.3%, p = 0.03). HGF-high expression (IHC score 2 or 3) was 33.3% in ALK(+) and 15.8% in ALK(−) (p = 0.17). We identified eight cases in ALK(−) and one case in ALK(+) tumor who had MET gene amplification (18.4% versus 7.1%, p = 0.43) by dual color, dual hapten bright field in situ hybridization. No significant correlation between MET protein receptor expression and gene amplification was identified.

Conclusions:

Our study demonstrated for the first time that MET receptor expression, but not MET gene amplification, is significantly increased in ALK(+) NSCLC. MET gene amplification is a relatively rare event in this unique population compared with ALK(−) NSCLC.

Copyright © 2014 by the International Association for the Study of Lung Cancer

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