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Could a mutational status of fibroblast growth factor receptor 3 (FGFR3) gene in bladder cancer tissue improve accuracy of clinical staging? Eur Urol Suppl 2013;12;e278
Rolevich A.I.1, Smal M.P.2, Krasny S.A.1, Goncharova R.I.2, Polyakov S.L.1, Nabebina T.I.1 1
N.N. Alexandrov National Cancer Centre of Belarus, Dept. of Urology, Minsk, Belarus, 2Institute of Genetics and
Cytology of National Academy of Sciences, Genetic Safety, Minsk, Belarus INTRODUCTION & OBJECTIVES: There is growing evidence supporting the significant prognostic value of FGFR3 gene mutation in urothelial bladder cancer (UBC). The ability of FGFR3 mutational status to improve the pathological stage prediction in patients with UBC is studied less. We have evaluated he association of FGFR3 gene mutational status with pathological muscle invasive disease and metastases in a prospective cohort of UBC patients with an adjustment to standard clinical variables. MATERIAL & METHODS: From 2009 to 2011 a total of 211 patients (165 males and 46 females) with a median age of 67 years were prospectively included it the study. The inclusion criteria were macroscopically evident bladder tumor at cystoscopy in a previously consented patient and pathologic confirmation of UBC after biopsy. The mutational status of tumor tissue was assessed with SNaPshot test in paraffin embedded samples after pathological examination and manual microdissection. The uni- and multivariate logistic regression analyses were used to assess the ability of standard clinical variables and FGFR3 mutational status to predict pathologically muscle-invasive (pT≥2) and metastatic (N+ and/or M+) disease. RESULTS: Clinically non-muscle invasive UBC was diagnosed in 149/211 (71%) patients, muscle invasive – in 62/211 (29%), pathologically non-muscle invasive UBC – in 140/211 (66%), muscle invasive – in 71/211 (34%). Regional and/or distal metastases were found in 17/211 (8%) patients. In the univariate logistic regression analysis cT category, age, macroscopic tumor appearance, tumor size, grade and и FGFR3 mutational status were associated with pT≥2, whereas gender, multifocality, previous recurrence rate and smoking were not. In multivariate model only clinical stage ≥T2 at cystoscopy (OR 35.4; 95%CI 13.1-96.2; pAs for metastatic disease cT, multifocality, tumor size, macroscopic appearance, grade and FGFR3 mutational status were found to be the significant variables in univariate analysis . However in multivariate model solid/ulcerative/necrotic appearance of the tumor (OR 17.0; 95%CI 1.3-222.6; p=0.031) was the only statistically significant factor predicting association with metastatic disease. CONCLUSIONS: In multivariate models the mutational status FGFR3 gene did not correlate with pathologically muscle invasive and metastatic disease. The mutational status of FGFR3 gene is no more accurate in the tumor extent prediction when comparing to standard clinical variables.