Lacroix Ludovic, Post Sophie F, Valent Alexander, Melkane Antoine E, Vielh Philippe, Egile Coumaran, Castell Christelle, Larois Christelle, Micallef Sandrine, Saulnier Patrick, Goulaouic Hélène, Lefebvre Anne-Marie, Temam Stéphane
Department of Medical Biology and Pathology, Institut Gustave Roussy, Villejuif, France ; Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France.
Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France ; Department of Plastic Surgery, University Medical Centre Groningen, Groningen, The Netherlands.
PLoS One. 2014 Jan 17;9(1):e84319. doi: 10.1371/journal.pone.0084319. eCollection 2014.
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.
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.
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.
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.
在口咽鳞状细胞癌（OPSCC）中鉴定MET基因改变、突变或扩增可能会促使MET选择性激酶抑制剂的研发。本研究的目的是评估原发性OPSCC中MET基因突变、扩增及蛋白表达的频率和预后价值。
对2007年1月至2009年12月期间接受单发性原发性OPSCC治疗的患者进行回顾性病历审查。分别使用桑格测序、荧光原位杂交（FISH）分析和免疫组化对治疗前的OPSCC组织样本进行MET突变、基因扩增及过表达分析。采用单因素和多因素分析来分析分子异常与患者生存之间的相关性。
本研究纳入了143例患者。鉴定出6例（4%）存在基因变异，但未检测到先前描述的突变，如p.Tyr1235Asp（Y1235D）或p.Tyr1230Cys（Y1230C）。有15例高多体性病例，仅有3例符合真正MET扩增的标准，即每例扩增细胞≥10%。免疫组化评估显示，43%的病例c-MET呈阴性，57%的病例在肿瘤细胞水平观察到c-MET。多因素分析显示MET突变、扩增或表达与生存之间无显著关联。
我们的研究表明，在该队列的OPSCC中，MET突变和扩增的频率较低。MET突变、扩增或表达与患者生存之间无显著相关性。这些结果表明，基于这些MET基因异常进行患者选择可能不是OPSCC治疗干预的可靠策略。
