CASTRATION THERAPY RAPIDLY INDUCES APOPTOSIS IN A MINORITY AND DECREASES CELL-PROLIFERATION IN A MAJORITY OF HUMAN PROSTATIC TUMORS

Major differences in the long-term clinical response to castration the rapy of prostatic carcinoma suggests intertumoral differences in cellu lar response and defines a need for identification of patients with an eventually positive outcome as well as those in need of additional tr eatment. Using morphometry, monoclonal antibodies against Bcl-2, c-myc , Ki-67, and p53 proteins, and an in situ method to visualize apoptoti c cells, we examined the short-term response of prostatic tumors to ca stration in core biopsies from 18 prostatic cancer patients taken the day before and 7 days after castration. At the histological level, 3 t umors seemed practically unaffected by castration. In 15 tumors, castr ation induced vacuolization of tumor cell cytoplasm and decreases in n uclear area and Ki-67 index In these 15 tumors, apoptotic index was si gnificantly increased in 6, principally unaffected ill 6, and decrease d in 3. The 6 tumors responding with an increase in apoptotic index we re WHO grade 1 or 2 and negative for p53, c-myc, and Bcl-2 or containe d only few Bcl-2- or c-myc-positive tumor cells before therapy. The 12 tumors in which apoptotic index was unaffected or decreased were WHO grade 2 or 3 and immunopositive fro one or more of p53, Bcl-2, and c-m yc proteins before therapy. The Bcl-2 index was significantly increase d in 10 patients. Prostatic tumors may respond in a variety of possibl y predictable ways to castration therapy including a decrease in apopt otic index. The magnitude of these responses are not correlated in ind ividual tumors, suggesting that the common classification of prostatic tumors as either androgen dependent (dying after castration) or indep endent (not responding at all to castration) may be an oversimplificat ion.