RESUMO
The aim of the study was to assess the genetic diversity of bladder cancer and determine the suitability of a proposed molecular marker panel to monitor the course of bladder cancer patients. The study involved 185 patients with diagnosed bladder cancer. The genetic diversity of the bladder cancer was evaluated by the prevalence of mutations in the TP53, HRAS, FGFR3 and WWOX genes. Mutations were detected in 62.2% of the tumor samples. The most frequently mutated genes were FGFR3 (49.7%) and TP53 (16.2%). No mutation was observed in the WWOX gene. FGFR3 mutations, contrary to TP53, correlated with lower tumor stage and grade, and the presence of multiple tumors. The risk of death was significantly higher in patients with TP53 mutant tumors (HR=3.12; 95%CI: 1.14-7.27; p=0.006) but lower in patients with FGFR3 mutations (HR=0.36; 95%CI: 0.15-0.87; p=0.002). None of the investigated genes was an independent predictor of disease-specific survival, recurrence-free survival or progression-free survival. The results confirm the existence of two alternative pathways of bladder cancer. However the presence of a high percentage of wild type variants in the higher stages of the disease suggest the existence of another pathway of molecular changes leading to the development of bladder cancer. Molecular analysis may have prognostic value and may facilitate the assignment of patients to appropriate forms of treatment - especially in the case of patients with a T1 tumor, where different mutational patterns were observed in each grade.
Assuntos
Variação Genética , Mutação , Neoplasias da Bexiga Urinária/genética , Humanos , Recidiva Local de Neoplasia , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Risco , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética , Neoplasias da Bexiga Urinária/terapia , Oxidorredutase com Domínios WW/genéticaRESUMO
Research was conducted on 220, 40 year old patients with a history of treatment for alcohol dependency. The prognosis of treatment effectiveness was based on a model of multiple regression. Five prognostic indices were discovered which explained 65% of total variation of the criterion variable.
