ТР53 GENE MUTATIONS AND THEIR PROGNOSTIC SIGNIFICANCE IN BLADDER CANCER

DOI: https://doi.org/None

M.P. Smal (1), A.I. Rolevich (2), Т.I. Nabebina (2), S.A. Krasny (2), R.I. Goncharova (1) 1 -Institute of Genetics and Cytology of the National Academy of Sciences of Belarus, Akademicheskaya str., 27, Minsk, 220072, Belarus; 2 -N.N. Alexandrov National Cancer Center of Belarus, Settlement Lesnoy, Minsky District, 223040, Belarus

Introduction. Mutations in the tumor suppressor gene TP53 are observed approximately in the half of all human malignancies. In bladder cancer (BC), ТР53 molecular alterations were shown to be associated with more aggressive tumor phenotype; however their clinical significance remains disputable. The aim of the study was to analyze the prognostic value of ТР53 mutation status with regard to bladder cancer recurrence, progression and mortality in a prospective cohort of BC patients. Methods. Molecular alterations in 5–8 exons of the TP53 gene were detected by PCR-SSCP followed by DNA sequencing. Results. TP53 mutations were found in 47 of 247 urothelial carcinomas (19,0%). TP53 mutations were strongly related to advanced tumor stage and grade, as well as non-papillary form of BC, large tumor size and the presence of metastasis. The assessment of the prognostic value of TP53 mutations showed their association with shorter progression-free survival and cancer-specific survival (CSS) in the whole group of patients. There were no statistically significant differences with regard to recurrence-free survival in terms of TP53 mutational status. Multivariate survival analysis using Cox regression model showed that 8 exon alterations were strong predictors of unfavourable outcome for patients with non-muscle invasive BC, whereas mutations in the 5th exon independently predicted decreased CSS in the group of patients with muscle-invasive disease. Conclusion. ТР53 gene mutation status is an independent prognostic factor for BC progression and mortality.
Keywords: 
bladder cancer, ТР53, mutation, prognosis
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