FGFR3, HRAS, KRAS, NRAS and PIK3CA Mutations in Bladder Cancer and Their Potential as Biomarkers for Surveillance and Therapy

摘要: textabstractBackground: Fifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies targeting receptor tyrosine kinases or activated oncogenes may improve outcome. Hence, it is necessary to stratify based on mutations in relevant oncogenes. Patients non-muscle-invasive (NMI-BC) have excellent survival, however two-thirds develop recurrences. Tumor specific can be used detect recurrences urine assays, presenting a more patient-friendly diagnostic procedure than cystoscopy. Methodology/Principal Findings: To address these issues, we developed mutation assay for the simultaneous detection 19 possible HRAS, KRAS, NRAS genes. With this assays FGFR3 PIK3CA oncogenes, screened primary tumors 257 184 54 patients. Additionally, p53 expression was obtained by immunohistochemistry. Of 64% were mutant FGFR3, 11% RAS, 24% PIK3CA, 26% p53. mutually exclusive RAS (p = 0.001) co-occurred 0.016). P53 overexpression (p≤0.029). Mutations genes not predictors recurrence-free, progression-free disease-specific In NMI-BC grade 3 MI-BC, 33 36% mutant. low-grade NMI-BC, 88% carried Conclusions/Significance: The present companion define targeted therapies. addition, are potential biomarker during surveillance. We showed that eligible such follow-up. This contribute reduction number cystoscopical examinations.