Background: Eunuchs rarely, if ever, develop prostate cancer (CaP). This article reports on a 62-year-old functional eunuch from prepubertal mumps orchitis who developed clinically localized CaP. Methods: Serum and CaP and benign prostate tissue androgen levels were measured using a validated liquid chromatography-tandem mass spectrometry assay. The assay measures testosterone; dihydrotestosterone (DHT); the adrenal androgens, androstenedione and dehydroepiandrosterone; and the androgen metabolites, androsterone and androstanedione. Gene and protein expression levels of androgen metabolism enzymes, and androgen receptor and androgen-regulated genes were measured using quantitative reverse-transcription polymerase chain reaction and immunohistochemistry, respectively. Results: Intracrine androgen metabolism produced tissue DHT when serum and tissue testosterone levels were castrate and undetectable, respectively. Androgen receptor, androgen-regulated, and androgen metabolism enzyme genes were expressed but at lower levels in CaP than benign tissues. Conclusions: DHT was synthesized using the primary backdoor androgen metabolism pathway and not using androstenedione or dehydroepiandrosterone via the frontdoor or secondary backdoor pathways.
These authors contributed equally to this manuscript.
Author Contributions:Radical prostatectomy procedure: Mohler. Supervision of experiment completion, data analysis, and manuscript development: Mohler. Execution of experiments, data analysis, manuscript development: Stocking and Fiandalo. Acquisition of paraffin-embedded tissues and performance of immunohistochemistry: Pop. Performance of all mass spectrometry measurements: Wilton. Characterization of prostate tissue: Azabdaftari. Assistance with data analysis: Wilton and Asabdaftari.
Correspondence: James L. Mohler, MD, Department of Urology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. E-mail: James.Mohler@RoswellPark.org