In:
Endocrine-Related Cancer, Bioscientifica, Vol. 16, No. 2 ( 2009-06), p. 443-453
Abstract:
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-FLIP L ) accounts for apoptosis resistance in a context of functional p53 and resistance could be overcome by c-FLIP L downmodulation. Here, we studied the association between c-FLIP L 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-FLIP L 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-FLIP L 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-FLIP L 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-FLIP L 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-FLIP L 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-FLIP L in refining the prognostic information obtained from standard clinical–pathological indicators, confirming its pivotal role in promoting cell survival.
Type of Medium:
Online Resource
ISSN:
1351-0088
,
1479-6821
Language:
Unknown
Publisher:
Bioscientifica
Publication Date:
2009
detail.hit.zdb_id:
2010895-3
