The impairment of apoptotic pathways represents an efficient mechanism to promote chemoresistance in cancer cells. We previously showed that in epithelial ovarian cancer (EOC) cells, long isoform of cellular FLICE-inhibitory protein (c-FLIPL) accounts for apoptosis resistance in a context of functional p53 and resistance could be overcome by c-FLIPL downmodulation. Here, we studied the association between c-FLIPL and p53 expressions and their prognostic impact in EOC patients. Tumor tissue from 207 patients diagnosed with primary EOC was analyzed by immunohistochemistry (IHC) for c-FLIPL and p53 expressions, and multiple correspondence analysis (MCA) was used to evaluate the multivariable pattern of association among patients' clinical-pathological characteristics and biological determinants. IHC revealed c-FLIPL expression and p53 nuclear accumulation inversely related (P=0.0001; odds ratio=0.29, confidence interval (CI)=0.15-0.055). MCA indicated that p53 accumulation was associated to clinical-pathological variables, while c-FLIPL expression contributed to the overall association pattern independently from other's clinical characteristics and complementary to p53. Kaplan-Meier curves showed a reduced survival time according to c-FLIPL expression in concert with p53 accumulation (median overall survival (OS): 35 months) compared with lack of expression of both markers (median OS: 110 months; log-rank test, P value=0.024). The multivariable Cox regression model, adjusted for known prognostic factors, identified c-FLIPL expression, but not p53 nuclear accumulation, as an independent prognostic factor for adverse outcome (hazard ratio=1.82, 95% CI=1.17-2.82; P=0.008). Altogether these data support the independent contribution of c-FLIPL in refining the prognostic information obtained from standard clinical-pathological indicators, confirming its pivotal role in promoting cell survival.
c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome / M. Bagnoli, F. Ambrogi, S. Pilotti, P. Alberti, A. Ditto, M. Barbareschi, E. Galligioni, E. Biganzoli, S. Canevari, D. Mezzanzanica. - In: ENDOCRINE-RELATED CANCER. - ISSN 1351-0088. - 16:2(2009), pp. 443-453.
|Titolo:||c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome|
|Settore Scientifico Disciplinare:||Settore MED/01 - Statistica Medica|
|Data di pubblicazione:||2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1677/ERC-08-0218|
|Appare nelle tipologie:||01 - Articolo su periodico|