High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer.
BACKGROUND
Activation of MET, either by increased gene copy number (GCN) or mutation, has been detected in various cancers. We investigate the clinicopathologic features of MET gene copy in nonsmall cell lung cancer (NSCLC).


METHODS
Tumor tissues were obtained from 180 resected NSCLCs, including 97 squamous cell carcinomas (SCCs) and 72 adenocarcinomas. No patient received epidermal growth factor receptor (EGFR)-targeted therapy. EGFR and MET GCNs were studied using fluorescence in situ hybridization (FISH) and were estimated according to the University of Colorado Cancer Center (UCCC) criteria. For MET, we also assessed GCNs using the Cappuzzo system.


RESULTS
FISH-positive MET was observed in 16.7% using the UCCC criteria; specifically, amplification was seen in 3.9% and high polysomy in 12.8%. FISH-positive MET status was significantly correlated with FISH-positive EGFR (p = 0.003). In the Cappuzzo system, high MET GCN (mean, >/=5 copies/cell) was found in 6.7% and also associated with FISH-positive EGFR (p = 0.031). MET gene copy status was not associated with gender, smoking history, histology, or stage. However, true MET amplification was more frequent in patients with SCC than in those with adenocarcinoma. FISH-positive MET status predicted worse survival in patients with NSCLC at advanced stages (p = 0.034) and in patients with SCC (p = 0.028). In multivariate analyses, increased MET GCN was significantly associated with shorter survival in patients with SCC, as analyzed using both the UCCC and Cappuzzo criteria (p = 0.019 and 0.008).


CONCLUSIONS
Our results suggest that increased MET GCN would be an independent poor prognostic factor in SCC of the lung.
Go
Heounjeong
H
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jeon
Yoon Kyung
YK
Park
Hyo Jin
HJ
Sung
Sook-Whan
SW
Seo
Jeong-Wook
JW
Chung
Doo Hyun
DH
D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate
D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met