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Involvement of the hepatocyte growth factor/scatter factor receptor c–met and of Bcl–x L in the resistance of oropharyngeal cancer to ionizing radiation
Author(s) -
Aebersold Daniel M.,
Kollar Attila,
Beer Karl T.,
Laissue Jean,
Greiner Richard H.,
Djonov Valentin
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010220)96:1<41::aid-ijc5>3.0.co;2-f
Subject(s) - hepatocyte growth factor , c met , receptor tyrosine kinase , cancer research , ionizing radiation , medicine , receptor , oncology , bcl xl , cancer , apoptosis , radiation therapy , survival analysis , signal transduction , biology , programmed cell death , irradiation , microbiology and biotechnology , biochemistry , physics , nuclear physics
The activation of cytoplasmic signal transduction pathways by a number of growth factors and their tyrosine–kinase receptors, including hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c–met, exerts an inhibitory influence on apoptosis induced by ionizing radiation in vitro . The clinical relevance of the aforementioned ligand–receptor pair, of Bcl–x L , which is targeted by HGF/SF/c–met signaling, and of Bcl–2, was assessed by evaluating their predictive and prognostic impact in a cohort of 97 patients with radically irradiated squamous cell cancers of the oropharynx. Immunohistochemical expression of c–met and Bcl–x L was correlated with decreased rates of complete remission of the primary tumor in both the univariate (c–met: P = 0.01; Bcl–x L : P = 0.001) and multivariate analyses. Expression of c–met was, moreover, a significant and independent predictor of impaired local failure–free survival ( P = 0.003), disease–free survival ( P = 0.003) and overall survival (p = 0.001). Bcl–2 expression was, on the other hand, associated with a favorable outcome, in terms of both local failure–free survival ( P = 0.01) and overall survival ( P = 0.001). In accordance with in vitro data, c–met and Bcl–x L appear to be involved in the resistance of oropharyngeal cancers to ionizing radiation, and may therefore represent attractive targets for radiosensitization. Int. J. Cancer (Radiat. Oncol. Invest.) 96, 41–54 (2001). © 2001 Wiley–Liss, Inc.