PROSTATIC TUMOR REGROWTH AFTER INITIALLY SUCCESSFUL CASTRATION THERAPY MAY BE RELATED TO A DECREASED APOPTOTIC CELL-DEATH RATE

Castration of rats transplanted with the androgen-sensitive Dunning R3 327-PAP prostatic tumor results initially in a reduction of tumor grow th, but after some time, some of the tumors start to grow again. The r elapsed, androgen-insensitive PAP tumor shows a dedifferentiated morph ology. In the present study, me examined whether this androgen-indepen dent tumor regrowth was due to an increased cell proliferation rate or to a reduction of the number of tumor cells dying by apoptosis. Nine rats (with 18 tumors) were castrated and followed for 16 to 20 weeks. Six of the tumors increased their volume markedly (relapsed), while 12 remained relatively stable (nonrelapsed). The mitotic index and apopt otic index for epithelial cells were examined by light microscopy. Tum or growth rate correlated negatively both to the apoptotic index ident ified by morphological criteria (RS = -0.82; P < 0.0001) and to the ap optotic index identified by in situ end labeling (RS = -0.83; P < 0.00 01). The tumor growth rate percentage did not correlate to the mitotic index, and it was negatively correlated (RS = -0.62; P < 0.01) to the number of cells immunostained for proliferating cell nuclear antigen. It is suggested that one initial event during the androgen-independen t prostatic tumor regrowth in the PAP relapse model might be a reducti on of the number of tumor cells being depleted by apoptosis, rather th an an increase of cell proliferation rate.