We recently identified activating mutations of fibroblast growth factor receptor 3 (FGFR3) in bladder carcinoma. In this study we assessed the incidence of FGFR3 mutations in a series of 132 bladder carcinomas: 20 carcinoma in situ (CIS), 50 pTa, 19 pT1, and 43 pT2-4. All 48 mutations identified were identical to the germinal activating mutations that cause thanatophoric dysplasia, a lethal form of dwarfism. The S249C mutation, found in 33 of the 48 mutated tumors, was the most common. The frequency of mutations was higher in pTa tumors (37 of 50, 74%) than in CIS (0 of 20, 0%; P < 0.0001), pT1 (4 of 19, 21%; P < 0.0001) and pT2-4 tumors (7 of 43, 16%; P < 0.0001). Bladder cancer is the fourth most common malignancy in men and the ninth most common in women in the Western world. In these countries, more than 90% of bladder tumors are urothelial carcinomas. At the time of initial diagnosis, approximately 80% of urothelial carcinomas are confined to the epithelium (pTa, CIS) or lamina propria (pT1), whereas the remaining 20% invade the muscularis propria (pT2, pT3, pT4). pTa lesions, the most common form of bladder carcinoma, are papillary tumors. Carcinoma in situ (CIS) are flat, cytologically highgrade carcinomas. Primary isolated CIS is a very rare entity, CIS being more commonly associated with other malignant bladder lesions. 1 Clinical evidence and molecular studies suggest that there are two pathways in bladder carcinogenesis responsible for generating two types of urothelium-confined tumors (pTa and CIS) with very different behavior. 1-6 pTa tumors are associated with a high rate of recurrence (50 -75%) but a low probability (Ͻ5%) of progression to lamina propria-invasive (pT1) and muscleinvasive (pT2-4) tumors. CIS may be the most common precursor of invasive bladder cancer because CIS shows a strong tendency to progress (40 -50%), and because most muscle-invasive lesions arise with no history of a pTa precursor lesion. This clinical evidence is supported by various molecular studies showing that CIS and invasive tumors have many genetic alterations in common, such as specific chromosomal deletions and a high frequency of p53 mutations. 2,7 In our search for new markers of carcinoma progression, we recently reported specific missense mutations in a gene encoding a growth factor receptor, fibroblast

In our study the depth of tumor invasion was a significant independent predictor of progression in patients with T1 bladder cancer. This result suggests that the depth of invasion in stage T1 should be included in the histopathological report.

In a selected transplant population with biopsy-proven CsA nephrotoxicity, CsA withdrawal with a concomitant switch from AZA to MMF seems to be safe and allows a significant improvement of renal function.

Because recent large studies have demonstrated that mycophenolate mofetil (MMF) is superior to azathioprine (AZA) as a posttransplant immunosuppressant, it has been speculated that MMF could have a cyclosporin (CsA)-sparing effect in renal transplant recipients with chronic allograft dysfunction. Between April 1996 and October 1998, 31 patients with chronic allograft dysfunction were assigned to have conversion from AZA to MMF with concomitant CsA withdrawal. Patient and graft outcomes were analysed. Mean follow-up time after MMF conversion was 27 * 11 months. Serum creatinine concentration (sCt) significantly decreased after conversion and remained stable at the end of followup (227 * 3 1 pmol/l vs. 185 It 50 pmol/l; P < 0.0005). Mean variation in sCt was -24% after conversion, whereas it was +20% in the year before conversion ( P < 0.001). There was a significant inverse relationship between proteinuria at baseline and improvement in renal function (r = -0.35; P = 0.01). Proteinuria increased during follow-up (0.79 It 0.6 vs.