Amplification of the androgen receptor gene is associated with P53 mutation in hormone-refractory recurrent prostate cancer.
p53 protein expression of 30 hormone-refractory locally recurrent prostate cancers was compared with their matched untreated primary tumour specimens. In addition, androgen receptor (AR) gene amplification and p53 protein immunostaining were compared. p53 positivity increased during hormonal therapy from 17 per cent of the untreated primary tumours to 40 per cent of the hormone-refractory recurrences (p = 0.078). None of the p53-positive primary tumour specimens lost p53 positivity during hormonal therapy. Hormone-refractory recurrences with AR gene amplification more frequently (p = 0.0342) showed positive p53 immunostaining than tumours without AR gene amplification, 75 and 27 per cent, respectively. In summary, this study has shown that a cell clone with P53 mutation seems to be selected for during endocrine therapy and that positive p53 immunostaining correlates with AR gene amplification. These results suggest that inactivation of P53 may lead to genetic instability in a subset of prostate carcinomas enabling them to achieve properties, such as AR gene amplification, that allow them to grow in low levels of androgens and therefore cause tumour progression.
Koivisto
P A
PA
Department of Clinical Chemistry, Tampere University Hospital, Finland.
Rantala
I
I
D000368:Aged; D018450:Disease Progression; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D011944:Receptors, Androgen / Q000235:genetics*; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D016159:Tumor Suppressor Protein p53