Correlation between MET protein expression and MET gene copy number in a Caucasian cohort of non-small cell lung cancers according to the new IASLC/ATS/ERS classification.
MET pathway is a promising target in non-small cell lung cancers (NSCLC) requiring companion tests. The aim of this study was to compare MET expression/gene copy number in a Caucasian population of NSCLC patients.We analysed 201 NSCLC, with 141 adenocarcinomas classified according to 2011 IASLC recommendations, for MET expression by immunohistochemistry (IHC) and gene copy number (GCN) by silver in situ hybridisation (SISH) on tissue microarrays. Mutations in EGFR, KRAS, BRAF, HER2, PIK3CA genes and ALK rearrangements were determined.MET overexpression was observed in 44% and a high MET GCN (≥5 copies) in 14%. MET CGN was correlated with MET expression, regardless of IHC scores (p < 0.001) but only 31% of MET overexpressed cases were SISH positive. MET overexpression/GCN number was more frequent in ADC than the other types (p < 0.001), the highest in high grade (74%/34%) and sarcomatoid ADC (86%/43%). Mutations of current genes or ALK rearrangements were identified in overexpressed or amplified MET cases. MET overexpression was an independent prognostic factor for overall survival in non-smoker NSCLC in univariate (p = 0.01) and multivariate (p = 0.01) analyses.MET overexpression is more frequent than MET high GCN, particularly in high grade ADC, regardless of EGFR, KRAS, BRAF, HER2, PIK3CA and ALK status in NSCLC.
1Department of Pathology, Strasbourg University Hospital 2Statistical Department, Strasbourg University Hospital 3Department of Biochemistry and Molecular Biology, Strasbourg University Hospital 4Research Unit EA 3430 and Translational Medicine Federation, Strasbourg University 5Department of Thoracic Surgery, Strasbourg University Hospital 6Chest Department, Strasbourg University Hospital 7Department of Pathology, Mulhouse Hospital 8Department of Pathology, Centre Paul Strauss Center, Strasbourg, France.
Noëlle
N
Weingertner
Nicolas
N
Meyer
Anne-Claire
AC
Voegeli
Dominique
D
Guenot
Stéphane
S
Renaud
Gilbert
G
Massard
Pierre-Emmanuel
PE
Falcoz
Anne
A
Olland
Bertrand
B
Mennecier
Marie-Pierre
MP
Gaub
Véronique
V
Lindner
Jean-Pierre
JP
Ghnassia
Elisabeth
E
Quoix
Marie-Pierre
MP
Chenard
Michèle
M
Beau-Faller
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D044465:White People
C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met