p53 alterations are predictive of chemoresistance and aggressiveness in ovarian carcinomas: a molecular and immunohistochemical study

Buttitta, Fiamma; Marchetti, Antonio; Gadducci, Angiolo; Pellegrini, Silvia; Morganti, M; Carnicelli, Vittoria; Cosio, Stefania; Gagetti, O; Genazzani, Andrea Riccardo; Bevilacqua, Generoso

doi:10.1038/bjc.1997.38

Cited by 131 publications

(89 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With respect to treatment, in this relatively small group of advanced ovarian cancer patients no association between TP53 expression or mutation and response to platinum-based chemotherapy was found. This is in agreement with data from previous immunohistochemical-based studies (Hartmann et al, 1994;Herod et al, 1996;Rohlke et al, 1997;van der Zee et al, 1995) but in contrast to other studies using either immunological (Dong et al, 1997;Ferrandina et al, 1999) or molecular-based techniques (Buttitta et al, 1997;Righetti et al, 1996).…”

Section: Discussionsupporting

confidence: 93%

Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2

Schuyer¹,

Burg²,

Henzen‐Logmans

et al. 2001

Br J Cancer

View full text Add to dashboard Cite

Summary Traditional clinicopathological features do not predict which patients will develop chemotherapy resistance. The TP53 gene is frequently altered in ovarian cancer but its prognostic implications are controversial. Little is known on the impact of TP53-downstream genes on prognosis. Using molecular and immunohistochemical analyses we examined TP53 and its downstream genes p21, BAX and BCL-2 in ovarian tumour tissues and have evaluated the results in relation to clinico-pathological parameters, clinical outcome and response to platinum-based chemotherapy. Associations of tested factors and patient and tumour characteristics were studied by Spearman rank correlation and Pearsons χ 2 test. The Cox proportional hazard model was used for univariate and multivariate analysis. The associations of tested factors with response was tested using logistic regression analysis. TP53 mutation, p21 and BCL-2 expression were not associated with increased rates of progression and death. Expression of TP53 was associated with a shorter overall survival only (relative hazard rate [RHR] 2.01, P = 0.03). Interestingly, when combining TP53 mutation and expression data, this resulted in an increased association with overall survival (P = 0.008). BAX expression was found to be associated with both progression-free (RHR 0.44, P = 0.05) and overall survival (RHR 0.42, P = 0.03). Those patients who simultaneously expressed BAX and BCL-2 had a longer progression-free and overall survival compared to patients whose tumours did not express BCL-2 (P = 0.05 and 0.015 respectively). No relations were observed between tested factors and response to platinum-based chemotherapy. We conclude that BAX expression may represent a prognostic indicator for patients with ovarian cancer and that the combined evaluation of BAX and BCL-2 may provide additional prognostic significance.

show abstract

Section: Discussionsupporting

confidence: 93%

Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2

Schuyer¹,

Burg²,

Henzen‐Logmans

et al. 2001

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…62 A clinical study of ovarian cancers also provides evidence that p53 mutations are associated with resistance to cisplatin-based chemotherapy. 63 In conclusion, there is ample in vitro and clinical evidence to show that p53 mutation is associated with resistance to chemotherapy in several cancer types. These findings support the introduction of TP53 mutation analysis in future clinical trials, possibly using high-throughput functional assays or microarray technology in order to reduce costs.…”

Section: Predictive Significance Of P53 Mutation In Cancer -Does It Amentioning

confidence: 97%

p53 and disease: when the guardian angel fails

2006

View full text Add to dashboard Cite

The p53 tumor suppressor gene (TP53) is mutated more often in human cancers than any other gene yet reported. Of importance, it is mutated frequently in the common human malignancies of the breast and colorectum and also, but less frequently, in other significant human cancers such as glioblastomas. There is also one inherited cancer predisposing syndrome called Li-Fraumeni that is caused by TP53 mutations. In this review, we discuss the significance of p53 mutations in some of the above tumors with a view to outlining how p53 contributes to malignant progression. We also discuss the usefulness of TP53 status as a prognostic marker and its role as a predictor of response to therapy. Finally, we outline some evidence that abnormalities in p53 function contribute to the etiology of other non-neoplastic diseases.

show abstract

“…Moreover, CDDP induces FLIP ubiquitination and degradation in a p53-and Itch-dependent manner (Abedini et al, 2008). The tumor-suppressor protein, p53, is a transcription factor regulating cell cycle, DNA repair and apoptosis, and is rapidly upregulated by DNA-damaging agents, including CDDP (Buttitta et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Akt promotes chemoresistance in human ovarian cancer cells by modulating cisplatin-induced, p53-dependent ubiquitination of FLICE-like inhibitory protein

et al. 2009

View full text Add to dashboard Cite

Although Akt is a determinant of cisplatin (cis-diaminedichloroplatinum (CDDP)) resistance in ovarian cancer cells, which is related in part to its inhibitory action on p53 activation, precisely how Akt confers CDDP resistance is unclear. In this study, we show that CDDP induced p53-dependent Fas-associated death domain-like interleukin-1b-converting enzyme (FLICE)-like inhibitory protein (FLIP) degradation in chemosensitive ovarian cancer cells but not their resistant counterparts. CDDP induced FLIP-p53-Itch interaction, colocalization and FLIP ubiquitination in chemosensitive but not chemoresistant ovarian cancer cells. Moreover, although activated Akt inhibited CDDP-induced FLIP degradation and apoptosis in sensitive cells, these responses were facilitated by dominant-negative Akt expression in chemoresistant cells. Inhibition of Akt function also facilitated p53-FLIP interaction and FLIP ubiquitination, which were attenuated by p53 silencing. These results suggest that Akt confers resistance, in part, by modulating CDDP-induced, p53-dependent FLIP ubiquitination. Understanding the precise etiology of chemoresistance may improve treatment for ovarian cancer.

show abstract

p53 alterations are predictive of chemoresistance and aggressiveness in ovarian carcinomas: a molecular and immunohistochemical study

Abstract: Summary Chemotherapeutic management of ovarian cancers is a difficult task as these neoplasms show significant differences in chemosensitivity, even

Cited by 131 publications

References 37 publications

Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2

Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2

p53 and disease: when the guardian angel fails

Akt promotes chemoresistance in human ovarian cancer cells by modulating cisplatin-induced, p53-dependent ubiquitination of FLICE-like inhibitory protein

Contact Info

Product

Resources

About