MP90-19 EXPRESSION OF MTOR PATHWAY PARAMETERS IN PROSTATE CANCER SHOWS SIGNIFICANT INTRATUMORAL HETEROGENEITY

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP90-19 EXPRESSION OF MTOR PATHWAY PARAMETERS IN PROSTATE CANCER SHOWS SIGNIFICANT INTRATUMORAL HETEROGENEITY Moritz Schanz, Jörg Hennenlotter, Johannes Dlugosch, Ursula Kuehs, Matthias Dettmer, David Schilling, Christian Schwentner, Arnulf Stenzl, and Tilman Todenhöfer Moritz SchanzMoritz Schanz More articles by this author , Jörg HennenlotterJörg Hennenlotter More articles by this author , Johannes DlugoschJohannes Dlugosch More articles by this author , Ursula KuehsUrsula Kuehs More articles by this author , Matthias DettmerMatthias Dettmer More articles by this author , David SchillingDavid Schilling More articles by this author , Christian SchwentnerChristian Schwentner More articles by this author , Arnulf StenzlArnulf Stenzl More articles by this author , and Tilman TodenhöferTilman Todenhöfer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2563AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In a high proportion of patients, prostate cancer (PC) is a multifocal disease. A high degree of inter- and intratumoral heterogeneity has been reported for several molecular alterations in previous studies. Aim of the present study was to analyze intratumoral heterogeneity of mTOR parameters by comparing the expression of these markers in different clearly defined areas of PC lesions. METHODS From radical prostatectomy specimens of 50 patients a tissue microarray including predefined areas of PC lesions and surrounding benign tissue was constructed (n=777 cores). Core localizations were determined starting from the tumor centre crossing the invasion front (TIF) into the benign prostatic tissue. Immunohistochemical reactive scores from mTOR, phospho(p)-mTOR and 4E-binding protein (4E-BP) were correlated to the topography of the analyzed tissue. RESULTS Mean expression Scores for mTOR in A) the tumor centre at least 10 mm away from the TIF, B) 6-10mm, C) 1-5 mm, D) inner border of TIF showing PC histology, E) outer border of TIF with benign histology, F) benign prostatic tissue 1-5 mm distant from the TIF, G) 10 mm distant and H) maximal apart were A: 5.714, B: 5.771, C: 6.026, D: 5.290, E: 5.220, F: 4.551 G: 4.986, H: 5.257. Mean expression scores of p-mTOR in areas A-H were A: 115.667, B: 75.571, C: 74.782, D: 70.759, E: 55.827, F: 34.644, G: 38.981 and H: 47.717 indicating a clear gradient from the tumor centre to the tumor periphery with overexpression of p-mTOR even in cancer-adjacent benign tissue. An expression gradient from the tumor centre across the tumor invasion front was also overved for 4-EBP with mean expression scores of A: 4.733, B: 4.303, C: 3.656, D: 3.310, E: 2.314, F: 2.284, G: 2.522 and H: 2.037. CONCLUSIONS In PC lesions, p-mTOR and 4E-BP show clear expression gradients with significant overexpression in tumor centres and consecutive decrease towards the TIF. Interestingly, the overexpression of the activated form p-mTOR even exceeds the TIF into benign tissue, whereas mTOR overexpression is limited to histologically malign tissue. These findings underline the importance of intratumoral heterogeneity of PC relevant protein parameters and have to been taken into consideration in studies addressing IHC parameters to identify diagnostic and prognostic markers. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1152 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Moritz Schanz More articles by this author Jörg Hennenlotter More articles by this author Johannes Dlugosch More articles by this author Ursula Kuehs More articles by this author Matthias Dettmer More articles by this author David Schilling More articles by this author Christian Schwentner More articles by this author Arnulf Stenzl More articles by this author Tilman Todenhöfer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...