Background:Angiogenesis is essential for tumour growth and metastasis. There are conflicting reports as to whether microvessel density (MVD) using the endothelial marker CD105 (cluster of differentiation molecule 105) in clear-cell renal cell carcinomas (ccRCC) is associated with prognosis. Recently, CD105 has been described as a RCC cancer stem cell marker.Methods:A total of 102 ccRCC were analysed. Representative tumour sections were stained for CD105. Vascularity (endothelial CD105) was quantified by MVD. The immunohistochemistry analysis detected positive (if present) or negative (if absent) CD105 tumoral staining. This retrospective population-based study was evaluated using Kaplan–Meier method, t-test and Cox proportional hazard model.Results:We found that the expression of endothelial CD105 (MVD) negatively correlated with nuclear grade (P<0.001), tumour stage (P<0.001) and Leibovitch score (P<0.001), whereas the expression of tumoral CD105 positively correlated with these three clinicopathological factors (P<0.001). In multivariate analysis, tumoral CD105 was found to be an independent predictor of poor overall survival (P=0.002).Conclusions:We have shown for the first time that tumoral CD105 is an independent predictive marker for death risk and unfavourable prognosis in patients with ccRCC after curative resection.

Hereditary cancers with cancer-predisposing mutations represent unique models of human oncogenesis as a driving oncogenic event is present in germline, exposing the healthy member of a family to the occurrence of cancer. The study of the secondary events in a tissue-specific manner is now possible by the induced pluripotent stem cell (iPSC) technology offering the possibility to generate an unlimited source of cells that can be induced to differentiate towards a tissue at risk of malignant transformation. We report here for the first time, the generation of a c-met-mutated iPSC lines from the somatic cells of a patient with type 1 papillary renal cell carcinoma (PRCC). We demonstrate the feasibility of kidney differentiation with iPSC-derived organoids expressing markers of kidney progenitors with presence of tight junctions and brush borders in tubular structures at transmission electron microscopy. Importantly, c-met-mutated kidney organoids expressed PRCC markers both in vitro and in vivo in NSG mice. Gene expression profiling of c-met-mutated iPSCderived organoid structures showed striking molecular similarities with signatures found in a large cohort of PRCC patient samples and identified 11 common genes. Among these, BHLHE40 and KDM4C, well-known factors involved in PRCC pathogenesis, were expressed in c-met-mutated kidney organoids. This analysis applied to primary cancers with and without c-met mutation showed overexpression of the BHLHE40 and KDM4C only in the c-met-mutated PRCC tumors, as predicted by c-met-mutated organoid transcriptome. These data represent therefore the first proof of concept of the generation of "renal carcinoma in a dish" model using c-met-mutated iPSC-derived organoids, opening new perspectives for discovery of novel potentially predictive disease markers and novel drugs for future precision medicine strategies. 3

The use of prostate biopsies was developed in parallel with progress in our knowledge of prostate cancer and the use of prostate-speci®c antigen (PSA). Prostate biopsies were initially indicated for the diagnosis of cancer, by the perineal approach under general anesthesia. Nowadays prostate biopsies are not only for diagnostic purposes but also to determine the prognosis, particularly before radical prostatectomy. They are performed in patients with elevated PSA levels, by the endorectal approach, sometimes under local anesthesia. (1±3) The gold standard is the sextant biopsy technique described by Hodge 4,5 , which is best to diagnose prostate cancer, particularly in case of T1c disease (patients with serum PSA elevation). 6±13 Patients with a strong suspicion of prostate cancer from a negative series of biopsies can undergo a second series IRYIS with transition zone biopsy 16,17 or lateral biopsy. 18,19 Karakiewicz et al 20 and Uzzo et al 21 proposed that the number of prostate biopsies should depend on prostate volume to improve the positivity rate. After the diagnosis of prostate cancer, initial therapy will depend on several prognostic factors. In the case of radical prostatectomy, the results of sextant biopsy provide a wealth of information. 22,23 The aim of this report is to present the information given by prostate biopsy in the staging of prostate cancer.