To elucidate the degree of androgen dependence in prostatic carcinoma, 5α-dihydrotestosterone (DHT) formation from testosterone in various histologic and cytologic features of the cancer tissue was studied.
Testosterone-
3H was incubated with 25mg of minces of prostatic needle biopsy specimens in the absence of coenzyme for one hour at 37°C in an atomosphere of 95 per cent of O
2 and 5 per cent of CO
2. Subsequently, the metabolites from testosterone were separated and purified with thin layer chromatography using a benzene acetone solvent system (4:1, v/v). The intracellular conversion rate of testosterone to DHT was employed as a biological marker for androgenic activity in the tissue of prostatic carcinoma.
Histologic findings of the carcinoma were evaluated by the method of Harada, Mostofi, et al. Histologic malignancy was divided into two groups, low and high grade, using various combination of histologic and cytologic analyses. Furthermore, the structural patterns of carcinoma were classified into five groups depending upon these predominant structual features, namely, a) single gland, b) cribriform, c) fused gland and cribriform, d) microgland, column and cord, e) medullarly, column and cord.
The results in the present paper were summarized as follows:
1) Average DHT formation was significantly higher in benign prostatic hypertrophy than in untreated prostatic carcinoma.
2) It should be born in mind that there are some patients who have the reactivation of prostatic carcinoma because of discontinuing hormonal treatment. The plasma testosterone concentrations of the patients were within the normal limit. (592±210ng/dl n=6)
Determination of plasma gonadotropin and testosterone levels can become a diagnostic step to find the false reactivation of prostatic carcinoma.
3) Similar degree of approximately 30per cent of the conversion rates of testosterone to DHT was observed in untreated prostatic carcinoma in the remissive status with hormonal therapy and in the false reactivation.
4) Histologically, low grade carcinoma showed statistically significant high conversion to DHT compared to high grade cancer.
5) The conversion rates to DHT in the groups of cases with single gland; cribriform; fused gland and cribriform; microgland, column and cord; and medullarly, column and cord were 40±8 (M±SD)% (n=4), 33±6 (n=3), 31±5 (n=7), 27±2 (n=3), and 15±4 (n=6), respectively.
Although the group with medullarly, column and cord pattern indicated significant lower conversion rate to DHT than the other histologic groups mentioned above, there existed correlation between the ability of DHT formation and structural patterns in the order highest in group a) and lowest in group e).
6) The findings of structural patterns in reactivated prostatic carcinoma showed the predominance features of medullarly and column & cord. However, there are, in part, single gland, microgland and cribriform. Consequently, reactivation has a wide spectrum of histologic patterns ranging from well to poor differentiation in a single specimen.
7) The reactivated prostatic carcinoma revealed the lowest ability of DHT formation in the tissue.
Getting together, it is suggested likely that histologic high grade of prostatic carcinoma and predominant features of medullarly, column and cord may imply relative androgen independent cancer, and that from the view of 5α-reductase activity, the reactivated prostatic carcinoma must be out of the control system in androgenic action. Furthermore, the assessment of 5α-reductase activity in combination with that of histologic and cytologic features in a biopsy specimen seemed to be a useful diagnostic tool in developing a prognosis and determining a suitable therapeutic program for prostatic carcinoma.
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