The aim of this study was to evaluate the expression levels of microRNAs (miRNAs) in bladder tumors in order to identify miRNAs involved in bladder carcinogenesis with potential prognostic implications. Expression levels of miRNAs were assessed by quantitative real-time RT-PCR in 11 human normal bladder and 166 bladder tumor samples (86 non-muscle-invasive bladder cancer (NMIBC) and 80 muscle-invasive bladder cancer (MIBC)). The expression level of 804 miRNAs was initially measured in a well-defined series of seven NMIBC, MIBC and normal bladder samples (screening set). The most strongly deregulated miRNAs in tumor samples compared to normal bladder tissue were then selected for RT-PCR validation in a well-characterized independent series of 152 bladder tumors (validation set), and in six bladder cancer cell lines. Expression levels of these miRNAs were tested for their association with clinical outcome. A robust group of 15 miRNAs was found to be significantly deregulated in bladder cancer. Except for two miRNAs, miR-146b and miR-9, which were specifically upregulated in MIBC, the majority of miRNAs (n 5 13) were deregulated in the same way in the two types of bladder tumors, irrespective of pathological stage : three miRNAs were upregulated (miR-200b, miR-182 and miR-138) and the other 10 miRNAs were downregulated (miR-1, miR-133a, miR-133b, miR-145, miR-143, miR-204, miR-921, miR-1281, miR-199a and miR-199b). A 3-miRNA signature (miR-9, miR-182 and miR-200b) was found to be related to MIBC tumor aggressiveness and was associated with both recurrence-free and overall survival in univariate analysis with a trend to significance in the multivariate analysis (p 5 0.05). Our results suggested a promising individual prognostic value of these new markers.

To our knowledge this is the first prospective, multicenter, phase II study showing that the platinum salts combination is an active and safe regimen as first line treatment in patients with metastatic collecting duct carcinoma. This platinum based chemotherapy should be considered the standard regimen in these patients.

Background: This study assessed the human epidermal growth factor receptor-2 (HER2) protein expression and its relationship with gene amplification in invasive bladder carcinoma, using the same criteria than for breast cancer.Patients and methods: In 1005 patients, paraffin-embedded tissues of transurethral resection or cystectomy were evaluated by immunohistochemistry (IHC), using antibodies against HER2. All samples with a 2+ or 3+ HER2 overexpression were evaluated by FISH.Results: HER2 overexpression was observed in 93 (9.2%) tumors (2+: 42 tumors and 3+: 51 tumors). Using FISH, all HER2 3+ tumors had a gene amplification, whereas no amplification was found in 2+ tumors. Intratumoral heterogeneity was observed in 35% of cases. These tumors showed the same heterogeneous pattern, with adjacent 3+ positive and negative areas by both IHC and FISH.Conclusions: This study showed that 5.1% of invasive bladder carcinomas had a HER2 gene amplification. These findings may have clinical implications for the management of patients with HER2-positive locally advanced or metastatic bladder cancer, as they could be potential candidates for targeted therapy.

Mucinous tubular and spindle cell carcinomas are low-grade renal epithelial neoplasms, which were first recognized as a specific entity in the World Health Organization 2004 classification. Forty-five documented cases have been reported. We present 15 additional cases that were incidentally discovered in ten women and five men, with a mean age of 53 years. The tumor is characteristically made up of large eosinophilic regular spindle cells separated by a myxoid stroma with intercellular alcian-blue-positive clear droplets. In peripheral areas, elongated tubules and papillae covered by cubic cells are found. Until this entity had been defined, pathologists used to classify these tumors as variants of solid papillary carcinomas with compressed and elongated papillae, metanephric adenomas, and sarcomatoid carcinomas. In the literature, cytogenetic data indicate various chromosomal losses and gains, but no loss of 3p or trisomy 7 and/or trisomy 17. In two cases, we demonstrate chromosomal loss involving chromosomes 1, 4, 6, 11, 8, 13, 14, 15, 18, and 22. In our 15 cases, immunohistochemistry favored a distal tubule origin (EMA(+), AE1/AE3(+), CK7(+), CK19(+), E-cadherin(+), AMACR(+), and CD10(-)). Prognosis was favorable in our cases, while in the literature, two metastatic cases were reported. Further investigations are required to determine the frequency and true prognosis of these tumors, which are easily identifiable morphologically.