Format

Send to

Choose Destination
PLoS One. 2014 Jan 17;9(1):e84319. doi: 10.1371/journal.pone.0084319. eCollection 2014.

MET genetic abnormalities unreliable for patient selection for therapeutic intervention in oropharyngeal squamous cell carcinoma.

Author information

1
Department of Medical Biology and Pathology, Institut Gustave Roussy, Villejuif, France ; Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France.
2
Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France ; Department of Plastic Surgery, University Medical Centre Groningen, Groningen, The Netherlands.
3
Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France.
4
Department of Oncology, Sanofi, Vitry-sur-Seine, France.
5
Department of Biologics Scientific Core Platform (BioSCP), Sanofi, Vitry-sur-Seine, France.
6
Department of Scientific Core Platform Clinical and Scientific Operations (SCP CSO), Sanofi, Vitry-sur-Seine, France.
7
Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France.

Abstract

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.

PMID:
24465403
PMCID:
PMC3894941
DOI:
10.1371/journal.pone.0084319
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center