Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation.
BACKGROUND
Mutations in the p53 gene resulting in the accumulation of altered p53 proteins with prolonged half-life have been found in a large variety of human malignancies.


OBJECTIVE
We studied the significance of p53 protein accumulation in prostatic carcinoma.


METHODS
The material consisted of 137 paraffin-embedded, primary prostatic carcinomas. Accumulation of p53 protein was studied by immunohistochemical staining using a polyclonal p53-specific CM-1 antibody. Proliferation activity was determined by DNA flow cytometry and by immunohistochemical detection of proliferative cell nuclear antigen (PCNA) using a monoclonal PC10 antibody.


RESULTS
Eight (6%) of the tumors showed intense p53 staining in more than 20% of the tumor cells, 15 (11%) had only lower level immunoreactivity, and 114 (83%) showed no staining. High-level p53 accumulation was associated with high histologic grade (P less than .001), DNA aneuploidy (P less than .05), and high cell proliferation rate as defined by flow cytometric S-phase analysis (P less than .01) or PCNA expression (P less than .01). High-level p53 accumulation predicted short, progression-free interval (P less than .01) and poor survival (P less than .001), with about a 12-fold relative risk of death as compared with p53-negative cases. Low-level p53 accumulation had no prognostic significance.


CONCLUSIONS
Accumulation of p53 confers proliferative advantage for prostatic carcinoma cells and defines a small subgroup of highly malignant carcinomas.
Department of Chemistry, Tampere University Hospital, Finland.
T
T
Visakorpi
O P
OP
Kallioniemi
A
A
Heikkinen
T
T
Koivula
J
J
Isola
D000368:Aged; D000906:Antibodies; D014408:Biomarkers, Tumor / Q000032:analysis*; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D005500:Follow-Up Studies; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012189:Retrospective Studies; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
D000906:Antibodies; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53