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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 5 2250-2257
Copyright © 2001 by The Endocrine Society

Original Studies

5{alpha}-Reductases in Human Breast Carcinoma: Possible Modulator of in Situ Androgenic Actions1

Takashi Suzuki, Andrew D. Darnel, Jun-Ichi Akahira, Naohiro Ariga, Sayaka Ogawa, Chika Kaneko, Junji Takeyama, Takuya Moriya and Hironobu Sasano

Department of Pathology, Tohoku University School of Medicine (T.S., A.D.D., J.-I.A., S.O., C.K., J.T., H.S.), and Department of Pathology, Tohoku University Hospital (N.A., T.M.), Sendai 980-8575, Japan

Address all correspondence and requests for reprints to: Takashi Suzuki, M.D., Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. E-mail: t-suzuki{at}patholo2.med.tohoku.ac.jp

The expression of 5{alpha}-reductase types 1 and 2 was examined in human breast carcinoma using immunohistochemistry and RT-PCR. Immunoreactivity for 5{alpha}-reductase isozymes was also correlated with various clinicopathological parameters to examine possible local regulatory mechanisms of sex steroids, including progesterone and androgens, in human breast carcinoma tissues. Immunoreactivity for 5{alpha}-reductase type 1 was detected in the cytoplasm and possibly in the nuclear membrane of tumor cells in 35 of 60 invasive ductal carcinomas (58%), and type 2 signal was detected in 9 of these 60 cases (15%). The results from RT-PCR (n = 8) were consistent with those from immunohistochemistry. A significant positive correlation was detected between 5{alpha}-reductase type 1 immunoreactivity and androgen and progesterone receptor A or B labeling indexes, and immunoreactivities of 5{alpha}-reductase type 2, 17ß-hydroxysteroid dehydrogenase type 5, or 3ß-hydroxysteroid dehydrogenase, which recognizes both types I and II. An inverse correlation was detected between 5{alpha}-reductase type 1 immunoreactivity and tumor size, histological grade, or Ki-67 labeling index. 5{alpha}-Reductase type 2 immunoreactivity was significantly correlated with 17ß-hydroxysteroid dehydrogenase type 5 immunoreactivity, but not with other parameters. This study suggests that 5{alpha}-reductase type 1 is mainly expressed in human breast carcinoma, which may play an important role in the in situ production and actions of the potent androgen, 5{alpha}-dihydrotestosterone, including inhibition of cancer cell proliferation, in hormone-dependent human breast carcinoma.




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