Summary There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, FLI1) or mutations (SPOP, FOXA1, IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1-mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

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Purpose: Epithelial to mesenchymal transition (EMT) is reportedly an important transition in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. In this study, we examined the expression pattern of EMT markers in vivo and determinedtheoccurrenceandclinicalsignificanceof these eventsinaseriesofbladdercarcinomas. Experimental Design: Eight hundred and twenty-five tumor samples from 572 bladder cancer patients were assembled in 10 tissue microarrays. Paraffin sections from each tissue microarray were subjected to antigen retrieval and processed by immunohistochemistry for the expression of E-cadherin, plakoglobin, h-catenin, N-cadherin, and vimentin. Results: Pathologic expression of E-cadherin, h-catenin, plakoglobin, and vimentin were associated with the clinicopathologic variables of grade and stage with only the cytoplasmic localization of plakoglobin found associated with lymph node status. Associations between the aforementioned markers were found significant as determined by the Spearman correlation coefficient with N-cadherin showing no associations in this analysis. In univariate survival analysis involving patients who underwent cystectomy, the reduction or loss of plakoglobin significantly influenced overall survival (P = 0.02) in which the median time to death was 2 years compared with 4 years when a normal level of plakoglobin was recorded. When the analysis was done for cancer-specific survival, low levels of both plakoglobin (P = 0.02) and h-catenin (P = 0.02) significantly influenced survival. Conclusion: The putative markers of EMTdefined within a panel of bladder carcinoma cell lines were recorded in vivo, frequently associated with tumors of high grade and stage. Although multivariate analysis showed no significant influence of the EMT biomarkers on survival, alterations associated with plakoglobin were identified as significant prognostic features in these tumors. Epithelial to mesenchymal transition (EMT) is a process thatwas first observed in embryonic development (1 -3) and has more recently been implicated as an underlying event in neoplastic progression (4 -7). To date, the definition and occurrence of EMT in in vivo tumorigenesis remains controversial (6, 8); however, the conceptual framework embracing loss of epithelial markers and gain of mesenchymal markers has been reportedly associated with numerous cancers (9 -11), often identified in cell lines established from tumors representing different grades and stage (10,12). In this way, the discontinuous progression model observed within a panel of cell lines of common tissue origin may be closely linked to the differentiation status of cells. In most cases, the projected transition between epithelial and mesenchymal phenotypes is accompanied by increased motility and invasive potential.With the advent of the establishment of in vitro models of EMT, elicited by the action of different factors on alternative cell types (13 -18), the existence of EMT in progression becomes mo...

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additional vesico-urethral anastomotic support. Patients in 2007 (182) received the total reconstructive procedure, which included an anterior reconstruction and posterior reconstruction. Outcome data were collected using standardized health-related quality-of-life measures, which included the Expanded Prostate Cancer Index Composite survey, International Prostate Symptom Score, International Index of Erectile Function, and then re-verified by telephone interview with a standardized questionnaire. The follow-up intervals were 1, 6, 12, 24 and 52 weeks. Continence was defined as no pad usage or one small liner used for security purposes only. Baseline variables were also collected. RESULTSThe percentage of patients who had achieved continence in the control group were: 13%, 35%, 50%, 62% and 82% at the 1-, 6-, 12-, 24-and 52-week follow-up, respectively. The percentage of patients who had achieved continence in the anterior reconstruction group were 27%, 59%, 77%, 86%, and 91%, respectively. The total reconstruction group had continence rates of 38%, 83%, 91%, and 97% at 1, 6, 12, and 24 weeks, respectively. At all the follow-up intervals the continence rate was significantly less in the control group than in the anterior reconstruction group and the total reconstruction group ( P < 0.01). CONCLUSIONSThe total reconstruction procedure is a safe and effective way to achieve an early return to continence. No adverse effects have been observed because of its employment and our data validates that it does provide a statistically significant early return to continence compared with no reconstructive efforts or with only anterior reconstructive efforts.