MET genetic abnormalities unreliable for patient selection for therapeutic intervention in oropharyngeal squamous cell carcinoma.
BACKGROUND
Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC.


METHODS
A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival.


RESULTS
143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p.Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were not detected. There were 15 high polysomy cases, and only 3 cases met the criteria for true MET amplification, with ≥10% amplified cells per case. Immunohistochemistry evaluation showed 43% of cases were c-MET negative and in 57% c-MET was observed at the tumor cell level. Multivariate analysis showed no significant association between MET mutation, amplification, or expression and survival.


CONCLUSIONS
Our study shows a low frequency of MET mutations and amplification in this cohort of OPSCC. There was no significant correlation between MET mutations, amplification, or expression and patient survival. These results suggest that patient selection based on these MET genetic abnormalities may not be a reliable strategy for therapeutic intervention in OPSCC.
Department of Medical Biology and Pathology, Institut Gustave Roussy, Villejuif, France ; Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France.
Ludovic
L
Lacroix
Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France ; Department of Plastic Surgery, University Medical Centre Groningen, Groningen, The Netherlands.
Sophie F
SF
Post
Department of Medical Biology and Pathology, Institut Gustave Roussy, Villejuif, France ; Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France.
Alexander
A
Valent
Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France.
Antoine E
AE
Melkane
Department of Medical Biology and Pathology, Institut Gustave Roussy, Villejuif, France ; Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France.
Philippe
P
Vielh
Department of Oncology, Sanofi, Vitry-sur-Seine, France.
Coumaran
C
Egile
Department of Oncology, Sanofi, Vitry-sur-Seine, France.
Christelle
C
Castell
Department of Biologics Scientific Core Platform (BioSCP), Sanofi, Vitry-sur-Seine, France.
Christelle
C
Larois
Department of Scientific Core Platform Clinical and Scientific Operations (SCP CSO), Sanofi, Vitry-sur-Seine, France.
Sandrine
S
Micallef
Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France.
Patrick
P
Saulnier
Department of Oncology, Sanofi, Vitry-sur-Seine, France.
Hélène
H
Goulaouic
Department of Biologics Scientific Core Platform (BioSCP), Sanofi, Vitry-sur-Seine, France.
Anne-Marie
AM
Lefebvre
Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France.
Stéphane
S
Temam
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D018579:Patient Selection; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D016019:Survival Analysis
C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met