Studies on Prostatic Cancer. I. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate

TLDR: It is demonstrated that a marked rise in acid phosphatase in serum is associated with the appearance or spread of roentgenologically demonstrable skeletal metastases and implies dissemination of the primary tumor and thus is of unfavorable prognostic significance.

Abstract: Carcinoma of the prostate gland is peculiarly favorable for endocrine investigation since frequent serial observations of the activity of phosphatases in serum were found to provide objective indices of activity of the neo/~i~m when the enzymes were increased in amount above normal. In the present paper data are given for the values of serum phosphatases in carcinoma of the prostate and in normal men. We shall demonstrate that the acid phosphatase of serum is reduced in metastatic carcinoma of the prostate by decreasing the activity of androgens through castration or estrogenic injections and that this enzyme is increased by injecting androgens. We have been unable to find previous observations indicating any relationship of hormones to carcinoma of the prostate gland. An enzyme capable of hydrolyzing phosphoric esters was discovered by Grosser and Husler (4) in intestinal mucosa and kidney. Robison (16) found that this enzyme was particularly high in activity in growing bone and cartilage and that its activity was greatest at pH 9 to 9.5. This ~alkaline phosphatase," was found by Kay (9) to be increased in the serum in certain bone diseases including metastasis of neoplasms to bone and later work has shown that among these conditions is carcinoma of the prostate. Davies (3) and Bamann and Riedel (1) discovered that there occurs in the spleen and kidney of swine and cattle, in addition to the alkaline phosphatase, a phosphatase with an activity maximum at pH 4.8. An enzyme believed to be identical with this "acid phosphatase" was found by Kutscher and Wolbergs (11) to be present in very large amount in the human prostate gland. This finding of great activity of acid phosphatase in the prostate gland was confirmed and extended to include prostatic cancer by Gutman, Sproul, and Gutman (7). The serum of certain patients with disseminated prostatic carcinoma was found by Gutman and Gutman (6) and Barringer and Woodard (2) to exhibit increased acid phosphatase activity. Robinson, Gutman, and Gutman'~I5) summarized the acid phosphatase activity levels of 44 patients with carcinoma of the prostate. They concluded that a marked rise in acid phosphatase in serum is associated with the appearance or spread of roentgenologically demonstrable skeletal metastases and implies dissemination of the primary tumor and thus is of unfavorable prognostic significance. METttODS AND MATERIALS