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
Dm. Aebersold et al., 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, INT J CANC, 96(1), 2001, pp. 41-54
The activation of cytoplasmic signal transduction pathways by a number of g
rowth factors and their tyrosine-kinase receptors, including hepatocyte gro
wth factor/scatter factor (HGF/SF) and its receptor c-met, exerts an inhibi
tory influence on apoptosis induced by ionizing radiation in vitro. The cli
nical relevance of the aforementioned ligand-receptor pair, of Bcl-x(L), wh
ich is targeted by HGF/SF/c-met signaling, and of Bcl-2, was assessed by ev
aluating their predictive and prognostic impact in a cohort of 97 patients
with radically irradiated squamous cell cancers of the oropharynx. Immunohi
stochemical 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 o
f 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 su
rvival (P = 0.01) and overall survival (P = 0.001). In accordance with in v
itro data, c-met and Bcl-xL appear to be involved in the resistance of orop
haryngeal cancers to ionizing radiation, and may therefore represent attrac
tive targets for radiosensitization.(C) 2001 Wiley-Liss, Inc.