Major differences in the long-term clinical response to
castration therapy of prostatic
carcinoma suggests intertumoral differences in cellular response and defines a need for identification of patients with an eventually positive outcome as well as those in need of additional treatment. Using morphometry,
monoclonal antibodies against Bcl-2, c-myc, Ki-67, and p53
proteins, and an in situ method to visualize apoptotic cells, we examined the short-term response of prostatic
tumors to
castration in core biopsies from 18
prostatic cancer patients taken the day before and 7 days after
castration. At the histological level, 3
tumors seemed practically unaffected by
castration. In 15
tumors,
castration induced vacuolization of
tumor cell cytoplasm and decreases in nuclear area and Ki-67 index. In these 15
tumors, apoptotic index was significantly increased in 6, principally unaffected in 6, and decreased in 3. The 6
tumors responding with an increase in apoptotic index were WHO grade 1 or 2 and negative for p53, c-myc, and Bcl-2 or contained 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 for one or more of p53, Bcl-2, and
c-myc proteins before
therapy. The Bcl-2 index was significantly increased in 10 patients. Prostatic
tumors may respond in a variety of possibly predictable ways to
castration therapy including a decrease in apoptotic index. The magnitude of these responses are not correlated in individual
tumors, suggesting that the common classification of prostatic
tumors as either
androgen dependent (dying after
castration) or independent (not responding at all to
castration) may be an oversimplification.