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RESEARCH PRODUCT
Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder.
Alina RomanenkoAlexander VozianovDavid RamosAndriy O. YurakhSilvia Calabuig-fariñasAntonio PellínEduardo SolsonaJosé RubioAntonio Llombart-boschJose Antonio López-guerrerosubject
OncologyMalemedicine.medical_specialtyUrologyCell Cycle ProteinsLoss of heterozygosityCyclin D1p14arfPredictive Value of TestsInternal medicineTumor Suppressor Protein p14ARFmedicineBiomarkers TumorHumansCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p15Univariate analysisBladder cancerbusiness.industryCarcinomaRetinoblastomaAnatomical pathologyProto-Oncogene Proteins c-mdm2Cell cyclemedicine.diseasePrognosisImmunohistochemistrySurvival AnalysisKi-67 AntigenMolecular Diagnostic TechniquesUrinary Bladder NeoplasmsCancer researchDisease ProgressionImmunohistochemistryFemaleNeoplasm Recurrence LocalTumor Suppressor Protein p53UrotheliumbusinessCyclin-Dependent Kinase Inhibitor p27description
Abstract Objective To evaluate the prognostic and predictive value of molecular and immunohistochemical markers related to cell-cycle control in terms of recurrence, progression, and survival in urothelial neoplasms of the bladder (UNB). Patients and Methods Clinical and pathological findings of 84 patients with UNB were assessed. Homozygous deletion (HD) and promoter methylation of p14 ARF , p15 INK4B , p16 INK4A , loss of heterozygosity of the locus 9p21, p53 mutations, and immunohistochemical expression of p53, p16, p14, p21, p27, pRb, Ki67, MDM2, and cyclin D1 proteins were evaluated in relation to overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). Results In the univariate analysis, RFS was shorter in cases with p14 ARF ( p =0.006), p15 INK4B ( p =0.003), p16 INK4A ( p =0.03) HD, low p14 immunoreactivity index (IRI) ( p =0.01) and high Ki67 IRI ( p =0.04); HD of the 9p21 locus genes and p14 IRI remained as independent prognostic factors for early UNB recurrence ( p =0.006) whereas tumour stage ( p =0.00001) and cyclin D1 IRI ( p =0.049) were related to worse PFS in the multivariate analysis. In the univariate analysis, IRI for Ki67 ( p =0.002), cyclin D1 ( p =0.06), p53 ( p =0.00008), p16 ( p =0.02), p27 ( p =0.0005) MDM2 ( p =0.01) and p53 mutations ( p =0.03) were related to poor OS, and only the Ki67 IRI retained their independent value in the multivariate analysis. Conclusion : 9p21 HD and p14 IRI constitute independent predictive factors for UNB recurrence and cyclin D1 IRI and tumour stage for progression. In addition, Ki67 IRI and tumour stage are independent prognostic factors for overall survival in UNB.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-09-01 | European urology |