Somatic mutation of fibroblast growth factor receptor-3 (FGFR3) defines a distinct morphological subtype of high-grade urothelial carcinoma.

摘要: FGFR3 mutations are common in low-grade urothelial carcinoma and represent a potential therapeutic target this disease. Their incidence functional role high-grade (HGUC), which displays an increased propensity for recurrence muscularis propria invasion, is less well defined. We developed mass spectrometry-based genotyping assay to define the of large clinically annotated set carcinomas. were found 17% HGUC versus 84% lesions. Retrospective pathological review class mutant revealed unique histological features, characterized by bulky, exophytic component with branching papillary architecture as irregular nuclei koilocytoid appearance. The predictive value appearance was confirmed using prospective 49 additional HGUCs. Prospective able correctly predict presence mutation 13/24 specimens that exhibited distinct morphology (54%). All 25 lacking defined features wild-type negative 100%. Macrodissection individual tumours allele non-invasive invasive, low regions lymph node metastases patients whose possessed characteristic morphological signature, suggesting not restricted more indolent These data suggest screening HGUCs followed confirmatory can be used enrich population most likely harbour activating FGFR-3 receptor tyrosine kinase. Histological could thus aid development targeted inhibitors facilitating identification subset gene.