You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2012316 SEMAPHORIN 4F AS A CRITICAL REGULATOR OF NEURO-EPITHELIAL INTERACTIONS AND A BIOMARKER OF AGGRESSIVE PROSTATE CANCER Gustavo Ayala, Yi Ding, Dandan He, Diego Florentin, Michael Ittmann, and David Rowley Gustavo AyalaGustavo Ayala Houston, TX More articles by this author , Yi DingYi Ding Houston, TX More articles by this author , Dandan HeDandan He Houston, TX More articles by this author , Diego FlorentinDiego Florentin Houston, TX More articles by this author , Michael IttmannMichael Ittmann Houston, TX More articles by this author , and David RowleyDavid Rowley Houston, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.376AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cancer related axono-neurogenesis is a recently described biologic phenomenon. Semaphorin 4F (S4F) is a member of family of proteins with roles in embryological axon guidance and is also expressed in adults. S4F produced by prostate cancer cells is a key regulator of the interactions between nerves in the tumor microenvironment and cancer cells. METHODS Tissue microarrays from radical prostatectomy specimens with PCa (350 patient) were immunostained with against S4F antibodies developed by us. Slides were imaged using image deconvolution imaging and analyzed using image segmentation technology. Data is provided on a cell per cell basis (nuclear vs. cytoplasmic), per tumor compartment, per patient. Data was correlated with pertinent clinico-pathological parameters, other biomarkers and survival analysis performed. To unders tand the heterogeneity of S4F expression we used an unsupervised clustering algorithm. RESULTS S4F expression was found in the cytoplasm and nuclei of epithelial PCa and reactive stromal cells and was over expressed in HGPIN/PCa than normal epithelium. Nuclear and cytoplasmic PCa and stromal S4F expression had differential expression patterns of heterogeneity. Patients with high values of S4F in PCa cytoplasm are at significantly higher risk of biochemical recurrence, by univariate and multivariate analysis (p=0.0007, HR=7.551 (2.34-24.31)). S4F cytoplasmic expression in PCa cells also correlates with nerve density in PCa (p=0.04) and perineural invasion diameter (p=0.004), corroborating involvement of this molecule in PCa induced axonogenesis and perineural invasion. Significant correlations were identified with NFkB and inversely with apoptosis in PNI. The cell-per-cell expression unsupervised clustering resulted in grouping of the patients with biochemical recurrence (fig 1), confirming that this novel way of measuring and analyzing biomarker has the potential to produce unique data. CONCLUSIONS This data demonstrates that S4F is significantly involved in human PCa progression and regulates the interaction between cancer and nerves. This also proves our ability to study biomarker expression within the reactive stroma and cancer compartments with state of the art quantitative methods. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e128 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gustavo Ayala Houston, TX More articles by this author Yi Ding Houston, TX More articles by this author Dandan He Houston, TX More articles by this author Diego Florentin Houston, TX More articles by this author Michael Ittmann Houston, TX More articles by this author David Rowley Houston, TX More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...
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