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Correlative study of the morphology and C19‐steroid metabolism of benign and cancerous human prostatic tissue
Author(s) -
Morfin Robert F.,
Leav Irwin,
Charles JeanFrancois,
Cavazos Lauro F.,
Ofner Peter,
Floch Hervé H.
Publication year - 1977
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(197704)39:4<1517::aid-cncr2820390425>3.0.co;2-#
Subject(s) - hyperplasia , dihydrotestosterone , prostate , adenocarcinoma , testosterone (patch) , malignant transformation , pathology , neoplastic transformation , endocrinology , cellular differentiation , hormone , medicine , chemistry , cancer , androgen , carcinogenesis , biochemistry , gene
Perineal punch biopsy specimens of human prostate with benign hyperplasia (BPH), well‐ and poorly‐differentiated adenocarcinoma and transitional‐cell carcinoma were incubated with testosterone‐1,2‐3H and 5α‐dihydrotestosterone‐1,2–3H. Incubations were carried out using a single tissue‐radiosubstrate ratio and time point. Resulting radiosteroid patterns were related to histologic and ultrastructural features of these tissues. Well differentiated neoplasms had ultrastructural characteristics closely resembling hyperplastic epithelia. Both in BPH and in well differentiated carcinomas the C19‐steroids were mainly metabolized by the 17β‐hydroxysteroid pathway. In contrast, cells in poorly‐differentiated adenocarcinoma and transitional‐cell carcinoma lacked the cytoplasmic organelles responsible for secretion; formation of 5α‐reduced 17β‐hydroxysteroids was decreased in these carcinomas, while conversion to 17‐oxosteroid radiometabolites remained unchanged or was greatly increased. These results indicate that loss of prostatic differentiation is attended by a trend from reductive toward oxidative radiotestosterone metabolism. Even in NADPH‐supplemented preparations of the majority of poorly‐differentiated tumors, there was diminished transformation to 5α‐dihydrotestosterone, the key intracellular hormone in the expression of androgenic activity in the prostate. These findings may explain why poorly‐differentiated prostatic neoplasms are frequently unresponsive to anti‐androgenic therapy.