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Prostatic Tumor Regrowth after Initially Successful Castration Therapy May Be Related to a Decreased Apoptotic Cell Death Rate¹

Departments of Pathology [M. L., A. B.] and Urology and Andrology [J-E. D.], University of Umeå, S-901 87 Umeå, Sweden

Castration of rats transplanted with the androgen-sensitive Dunning R3327-PAP prostatic tumor results initially in a reduction of tumor growth, but after some time, some of the tumors start to grow again. The relapsed, androgen-insensitive PAP tumor shows a dedifferentiated morphology. In the present study, we examined whether this androgen-independent 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 apoptotic index for epithelial cells were examined by light microscopy. Tumor growth rate correlated negatively both to the apoptotic index identified by morphological criteria (RS = -0.82; P < 0.0001) and to the apoptotic index identified by in situ end labeling (RS = -0.83; P < 0.0001). 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-independent prostatic tumor regrowth in the PAP relapse model might be a reduction of the number of tumor cells being depleted by apoptosis, rather than an increase of cell proliferation rate.

¹ This work is supported by the Swedish Cancer Society (Project No. 1760), The Swedish Society of Medicine, the Lion's Research Foundation, the Maud and Birger Gustavsson Foundation, the Magnus Bergvalls Foundation, the Dagmar Ferb Foundation, and the Sahlberg Foundation.

² To whom requests for reprints should be addressed.

Received 5/ 6/94. Accepted 7/ 5/94.

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