Anti-androgen therapy has been used widely for prostatic cancer, without constant success. In addition, there are some cases which respond to the therapy initially but do not later. Since androgen acts via androgen receptors (AR) in the target cells, the presence of AR in the tissue of prostatic cancer must be essential for effectiveness of the anti-androgen therapy to the cancer.
Previously we reported a method to detect the localization of AR within the human prostatic tissues by means of autoradiography. We examined the localization of AR in the prostatic cancers and investigated the relationship between AR and effectiveness of the hormone therapy and between AR and pathological grade of prostatic cancers.
12 prostatic cancer tissues and one metastatic lymph node tissue were obtained by needle biopsy from 10 patients. Cryostat-frozen sections of the tissues were cut at 10μm thick, air-dried, fixed in 10% formalin in PBS (pH7.4) for 5 minutes and washed in three baths of PBS. The tissue sections were trated with 50μl of 100nM tritiated dihydrotestosterone (
3H-DHT) in a humid box at room temperature for two hours, washed and air-dried. The sections were then dipped into Sakura NRM-2 autoradiographic emulsion, dried at room temperature, followed by dipping into scintillator solution consisted of 7% PPO and 0.02% POPOP dissolved in dioxan and exposed in the dark for two weeks. After exposure the emulsion sheets covering the sections were developed, and the sections were stained with hematoxylin.
By autoradiography we examined AR in the prostatic cancers and got the following conclusions:
1) There are three types of prostatic cancers. The first type of the cancers consists of AR positive cells only, the second type consists of AR negative cells only, and the third type consists of both AR positive cells and AR netative cells.
2) In the prostatic cancer tissues with AR positive cells and AR negative cells, each group of cells forms a mass of various size.
3) With regard to the relationship between AR and pathological grade of cancers, of 4 cancers with AR positive cells, one was well differentiated adenocarcinoma, two were moderately differentiated adenocarcinomas and one was poorly differentiated adenocarcinoma. On the other hand, of 3 cancers with AR positivecells and AR negative cells, one was of moderately differentiated type and three were of poorly differentiated types. And 2 cancers with AR negative cells were both of poorly differentiated type.
4) With regard to the relationship between AR and effectiveness of anti-androgen therapy, of 4 cancers with AR positive cells, all four responded to the therapy. Of 4 cancers with AR positive cells and AR negative cells, three (75%) responded. And of 2 cancers with AR negative cells, one (50%) responded.
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