Molecular grading of tumors of the upper urothelial tract using FGFR3 mutation status identifies patients with favorable prognosis

Stephen R Lyle,1 Chung-Cheng Hsieh,1 Cecilia A Fernandez,2 Anthony P Shuber21University of Massachusetts, Worcester, MA, 2Predictive Biosciences Inc., Lexington, MA, USABackground: Mutations in FGFR3 have been shown to occur in tumors of the upper urothelial tract and may be indicative of a good prognosis. In bladder tumors, the combination of FGFR3 mutation status and Ki-67 level has been used to define a tumor's molecular grade and predict survival. Pathological evaluation of upper urothelial tumors is currently the best predictor of prognosis, but suffers from variability in pathological assessments. This study investigated the association with prognosis of FGFR3 mutations alone and in combination with Ki-67 in this patient population.Methods: Genomic DNA was isolated from tumor samples of 80 patients with upper urothelial cancer. The presence of mutation in FGFR3 was evaluated using real-time polymerase chain reaction. Ki-67 protein expression was determined by immunohistochemistry. Kaplan–Meier survival analysis evaluated the relationship of FGFR3 mutations and Ki-67 levels with survival.Results: FGFR3 mutations were identified in 40% of tumors and were predominantly associated with noninvasive tumors. Overall survival was higher in patients with FGFR3 mutant tumors (P = 0.02) and in molecular grade 1 tumors as determined by FGFR3 and Ki-67 (P = 0.02).Conclusion: In this study, we confirm the occurrence of FGFR3 mutations in tumors of the upper urothelial tract and its association with a good prognosis. Both FGFR3 and molecular grading are predictors of overall survival. Molecular grading can help to assess the prognosis of patients with upper urinary tract cancer and may represent a new tool for managing this population of patients.Keywords: upper tract, urothelial carcinoma, ureter, renal pelvis, Ki-67, survival