INCREASED CELL-PROLIFERATION ACTIVITY AND DECREASED CELL-DEATH ARE ASSOCIATED WITH THE EMERGENCE OF HORMONE-REFRACTORY RECURRENT PROSTATE-CANCER

The tumour growth kinetics (cell proliferation and apoptosis) of ten h ormone-refractory locally recurrent prostate cancers were compared wit h their matched untreated primary tumour specimens, AU recurrent tumou rs had a higher cell proliferation activity, as defined by Ki-67 immun ohistochemistry, than corresponding primary tumours from the same pati ents, The mean cell proliferation activity in recurrences (13.5+/-3.8 per cent) was over two times higher (P<0.0001) than that in primary tu mours (5.5+/-2.4 per cent), suggesting that cell clones which progress during androgen withdrawal are actively stimulated to proliferate. Th e mean percentage of apoptotic cells, as estimated by the in situ end- labelling technique, was 5.4+/-4.7 per cent in untreated primary tumou rs, whereas it was 2.3+/-1.5 per cent in locally recurrent tumours (P= 0.05). In all but two cases, the apoptotic index was lower in recurren t than in corresponding primary tumours, suggesting that recurrent pro state carcinomas are able to avoid apoptosis in the androgen-deprived environment, In conclusion, the clinical progression of prostate cance r during androgen withdrawal is associated with increased cell prolife ration and decreased apoptosis. (C) 1997 by John Wiley & Sons, Ltd.