MP62-11 CHARACTERIZATION OF PROSTATE CANCER IN A FUNCTIONAL EUNUCH

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2016MP62-11 CHARACTERIZATION OF PROSTATE CANCER IN A FUNCTIONAL EUNUCH Michael Fiandalo, John Stocking, Elena Pop, John Wilton, Gissou Azabdaftari, and James Mohler Michael FiandaloMichael Fiandalo More articles by this author , John StockingJohn Stocking More articles by this author , Elena PopElena Pop More articles by this author , John WiltonJohn Wilton More articles by this author , Gissou AzabdaftariGissou Azabdaftari More articles by this author , and James MohlerJames Mohler More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.919AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (CaP) development and growth rely on androgen receptor (AR) and its ligands, testosterone (T) and dihydrotestosterone (DHT). CaP that recurs in spite of castrate levels of circulating T has been shown to contain levels of T and DHT sufficient for AR transactivation that are produced by intratumoral intracrine metabolism. We report a case of CaP that developed in a functional eunuch male, which provided the opportunity to characterize fully serum and prostate tissue androgen levels and gene and protein expression profiles. Patient suffered mumps orchitis at age 13, developed secondary sex characteristics poorly, was married briefly and never fathered a child. T replacement therapy (TRT) was begun to treat hypogonadal symptoms at age 60 when prostate exam was benign, prostate-specific antigen (PSA) was 0.43 ug/dl and PSA doubling time was 3.18 years. TRT was halted and prostate biopsy using transrectal prostate ultrasound (TRUS) revealed a 14.6 g prostate with Gleason grade 4+4=8 adenocarcinoma. Radical prostatectomy revealed Gleason grade 3+4=7 (PT3aN0) CaP that invaded bladder neck but surgical margins were negative. PSA was low detectable 2 years later. METHODS Serum, CaP and benign prostate tissue androgen levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The assay measures T, DHT, the adrenal androgens androstenedione (ASD) and dehydroepiandrosterone and the androgen metabolite, androsterone. Androgen metabolism enzyme, AR and AR-regulated gene expression levels were measured using qRT-PCR and immunohistochemistry (IHC) for protein. RESULTS LC-MS/MS showed that T was not measurable in benign prostate or CaP tissues. DHT levels were higher in benign prostate than CaP tissues. Serum T, DHT and ASD levels were at the limit of detection. Androgen metabolism enzyme gene and AR and AR-regulated gene and protein expression levels were lower in CaP than benign tissues. CONCLUSIONS Androgen levels, AR and AR-gene expression levels were lower in CaP than benign prostate tissues, which is similar to what investigators have reported for castration-recurrent CaP. The benign prostate had no T and low ASD levels, which suggest that the benign prostate may have used the primary backdoor androgen metabolism pathway to generate DHT. The benign prostate grew in a castrate microenvironment and may have created a microenvironment conducive for growth of CaP with characteristics of castration-recurrent instead of androgen-stimulated CaP. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e816 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Michael Fiandalo More articles by this author John Stocking More articles by this author Elena Pop More articles by this author John Wilton More articles by this author Gissou Azabdaftari More articles by this author James Mohler More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...