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 hormone-refractory locally recurrent prostate cancers were compared with their matched untreated primary tumour specimens. All recurrent tumours had a higher cell proliferation activity, as defined by Ki-67 immunohistochemistry, than corresponding primary tumours from the same patients. 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 tumours (5.5 +/- 2.4 per cent), suggesting that cell clones which progress during androgen withdrawal are actively stimulated to proliferate. The mean percentage of apoptotic cells, as estimated by the in situ end-labelling technique, was 5.4 +/- 4.7 per cent in untreated primary tumours, 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 recurrent than in corresponding primary tumours, suggesting that recurrent prostate carcinomas are able to avoid apoptosis in the androgen-deprived environment. In conclusion, the clinical progression of prostate cancer during androgen withdrawal is associated with increased cell proliferation and decreased apoptosis.
Koivisto
P
P
Laboratory of Cancer Genetics, University of Tampere, Finland. blpako@uta.fi
Visakorpi
T
T
Rantala
I
I
Isola
J
J
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D017209:Apoptosis; D002455:Cell Division; D018450:Disease Progression; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000473:pathology* / Q000628:therapy; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology* / Q000628:therapy; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy; D017211:Treatment Failure
D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen