Cell cycle regulators in bladder cancer: A multivariate survival study with emphasis on p27Kip1

Korkolopoulou, P; Christodoulou, P; Konstantinidou, AE; Thomas-Tsagli, E; Kapralos, P; Davaris, P

dc.contributor.author	Korkolopoulou, P	en
dc.contributor.author	Christodoulou, P	en
dc.contributor.author	Konstantinidou, AE	en
dc.contributor.author	Thomas-Tsagli, E	en
dc.contributor.author	Kapralos, P	en
dc.contributor.author	Davaris, P	en
dc.date.accessioned	2014-03-01T01:49:46Z
dc.date.available	2014-03-01T01:49:46Z
dc.date.issued	2000	en
dc.identifier.issn	0046-8177	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/25919
dc.subject	p21	en
dc.subject	p27	en
dc.subject	p16	en
dc.subject	pRb	en
dc.subject	bladder cancer	en
dc.subject.classification	Pathology	en
dc.subject.other	DEPENDENT KINASE INHIBITOR	en
dc.subject.other	PROTEIN EXPRESSION	en
dc.subject.other	PROGNOSTIC VALUE	en
dc.subject.other	P27(KIP1) EXPRESSION	en
dc.subject.other	POTENTIAL MEDIATOR	en
dc.subject.other	TUMOR PROGRESSION	en
dc.subject.other	SUPPRESSOR GENES	en
dc.subject.other	P53	en
dc.subject.other	CARCINOMA	en
dc.subject.other	P27	en
dc.title	Cell cycle regulators in bladder cancer: A multivariate survival study with emphasis on p27Kip1	en
heal.type	journalArticle	en
heal.language	English	en
heal.publicationDate	2000	en
heal.abstract	Cyclin-dependent kinase inhibitors (CKIs) prevent cyclin-dependent kinases from phosphorylating critical substrates such as retinoblastoma gene protein (pRb), hence blocking the cascade of events leading to cell proliferation. Currently, the list of CKIs includes p21WAF1/Cip1, p27Kip1, p57Kip2 (the Cip/Kip family), p15/INK4b, p16/INK4a, p18/INK4c, and p19/INK4d (the INK4 family). Among them, p27 plays a crucial role inning extracellular growth-regulatory signals to progression to or exit from the cell cycle. Unlike p53, p16, and Rb, mutations in Kip1 and WAF1 genes are distinctly rare in bladder cancer. We analyzed immunohistochemically the expression of p27 and other interacting G1 proteins (ie, p21, p16, pRb, p53) in 120 consecutive cases of transitional cell carcinomas (TCCs) and related it to proliferation rate, clinicopathologic parameters, and survival. p27 levels were significantly higher in low-grade (P = .001), superficial (Ta-T1) (P = .001), papillary (P < .001), and slowly proliferating TCCs (r(s) = -0.235, P = .05). p27 also positively correlated with p16 expression (r(s) = 0.212, P = .05). In univariate analysis, decreased p27 expression was associated with poor overall (P = .0100) and postrelapse (P = .0344) survival, especially if combined to increased Ki-67 expression (P = .0004 and P = .036, respectively). Furthermore, in multivariate analysis, Ki-67/p27 status had the strongest hearing on the overall survival of muscle-invasive TCCs (P = .0019). Our results indicate that low p27 expression is more common in poorly differentiated muscle-invasive TCCs and is a major player in cell cycle control in these neoplasms. More importantly, the combined Ki-67/p27 expression provides prognostic information beyond that provided by conventional parameters or other cell cycle-related proteins, concerning overall survival in muscle-invasive TCCs. HUM PATHOL 31:751-760. Copyright (C) 2000 by W.B. Saunders Company.	en
heal.publisher	W B SAUNDERS CO	en
heal.journalName	HUMAN PATHOLOGY	en
dc.identifier.isi	ISI:000087692100019	en
dc.identifier.volume	31	en
dc.identifier.issue	6	en
dc.identifier.spage	751	en
dc.identifier.epage	760	en