P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens

Plisiecka-Hałasa, Joanna; Karpińska, G; Szymanska, T.; Ziółkowska, Iwona; Mądry, Radosław; Timorek, Agnieszka; Dȩbniak, Jarosław; Ułańska, Małgorzata; Jędryka, Marcin; Chudecka‐Głaz, Anita; Klimek, Małgorzata; Rembiszewska, Alina; Kraszewska, Ewa; Dybowski, Bartosz; Markowska, Janina; Emerich, Janusz; Płużańska, A; Goluda, M; Rzepka-Górska, I; Urbański, Krzysztof; Zieliński, J; Stelmachów, J; Chrabowska, M.; Kupryjańczyk, Jolanta

doi:10.1093/annonc/mdg299

Cited by 45 publications

(36 citation statements)

References 26 publications

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“…Inactivation of p53 function leads to loss of p21 Waf1/Cip1 induction and impairment of cyclin/CDK complex inhibition. Indeed, we found that 77% of serous EOC in our cohort had low or no expression of p21 Waf1/Cip1 , which was significantly associated with poor survival and a shorter progression-free interval, as previously demonstrated by others (41)(42)(43)(44). In addition, we found significant loss of p21 Waf1/Cip1 expression in tumors that overexpressed p53, although this did not seem to be the case in all tumors.…”

Section: Loss Of P16supporting

confidence: 86%

Cyclin D1, p53, and p21Waf1/Cip1 Expression Is Predictive of Poor Clinical Outcome in Serous Epithelial Ovarian Cancer

Bali

O’Brien

Edwards

et al. 2004

Clinical Cancer Research

138

124

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Purpose: Dysregulation of cell cycle control, in particular G 1 -S-phase transition, is implicated in the pathogenesis of most human cancers, including epithelial ovarian cancer (EOC). However, the prognostic significance of aberrant cell cycle gene expression in EOC remains unclear.Experimental Design: The expression of selected genes from the pRb pathway that regulates G 1 -S-phase progression, including cyclin D1, p16Ink4a , cyclin E, p27 Kip1 , p21Waf1/Cip1 , and p53, was examined in a consecutive series of 134 serous EOC using immunohistochemistry and the results correlated to disease outcome.Results: Molecular markers predictive of reduced overall survival in univariate analysis were overexpression of cyclin D1 (P ‫؍‬ 0.03) and p53 (P ‫؍‬ 0.03) and reduced expression of p27 Kip1 (P ‫؍‬ 0.05) and p21 Waf1/Cip1 (P ‫؍‬ 0.02), with the latter three also being prognostic for a shorter progression-free interval. In addition, patients displaying overexpression of p53 with concurrent loss of p21 Waf1/Cip1 had a significantly shorter overall (P ‫؍‬ 0.0008) and progression-free survival (P ‫؍‬ 0.0001). On multivariate analysis, overexpression of cyclin D1 and combined loss of p21 Waf1/Cip1 in the presence of p53 overexpression were independent predictors of overall survival. Similarly, the combination of p21 Waf1/Cip1 loss and p53 overexpression was independently predictive of a shorter progression-free interval. Overexpression of p53 and cyclin E and reduced expression of p27Kip1 and p21 Waf1/Cip1 were significantly associated with increasing tumor grade.Conclusions: This study confirms that dysregulation of cell cycle genes is common in EOC, and that aberrant expression of critical cell cycle regulatory proteins can predict patient outcome in serous EOC.

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Section: Loss Of P16supporting

confidence: 86%

Cyclin D1, p53, and p21Waf1/Cip1 Expression Is Predictive of Poor Clinical Outcome in Serous Epithelial Ovarian Cancer

Bali

O’Brien

Edwards

et al. 2004

Clinical Cancer Research

138

124

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“…Baekelandt et al (1999) found no correlation between expression of p21 and p27 in ovarian cancer and response to chemotherapy with epirubicin and cisplatin. Another study showed in vivo a better response to platinum based chemotherapy with high p21 expression in ovarian cancer (Plisiecka-Halasa et al 2003). Our study could not prove any association between expression of cki p21 and p27 and chemotherapy response, but only a small subgroup of our patients could be evaluated and the number of patients for statistical analysis is very small.…”

Section: Multivariate Analysis For Prognostic Factorsmentioning

confidence: 63%

Cyclin-dependant kinase inhibitors CIP1 (p21) and KIP1 (p27) in ovarian cancer

Schmider‐Ross

Pirsig

Gottschalk

et al. 2005

J Cancer Res Clin Oncol

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“…Similarly, decreased p27 expression (as reported in 55% of OC), showed an independent association with poor survival in patients with advanced OC [10]. The simultaneous assessment of multiple cyclerelated proteins could be particularly useful in the prognostic stratification of OC [4,9].…”

Section: Loss Of Cell Proliferation Controlmentioning

confidence: 94%

“…Concerning with the CDK inhibitors, the expression of p21 is lost in 25-75% of OC [4,7,8] and low p21 expression is associated with: high tumor grade [4], advanced stage and residual tumor after surgery [7], and low response rate to platinum-based chemotherapy [9]. Similarly, decreased p27 expression (as reported in 55% of OC), showed an independent association with poor survival in patients with advanced OC [10].…”

Section: Loss Of Cell Proliferation Controlmentioning

confidence: 99%

Biological characterization of ovarian cancer: prognostic and therapeutic implications

Legge¹,

Ferrandina²,

Salutari³

et al. 2005

Annals of Oncology

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P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens

Cited by 45 publications

References 26 publications

Cyclin D1, p53, and p21Waf1/Cip1 Expression Is Predictive of Poor Clinical Outcome in Serous Epithelial Ovarian Cancer

Cyclin D1, p53, and p21Waf1/Cip1 Expression Is Predictive of Poor Clinical Outcome in Serous Epithelial Ovarian Cancer

Cyclin-dependant kinase inhibitors CIP1 (p21) and KIP1 (p27) in ovarian cancer

Biological characterization of ovarian cancer: prognostic and therapeutic implications

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