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 imm unostaining were compared. p53 positivity increased during hormonal therapy from 17 per cent of the untreated primary tumours to 40 per cent of the ho rmone-refractory recurrences (p=0.078). None of the p53-positive primary tu mour specimens lost p53 positivity during hormonal therapy, Hormonere-fract ory recurrences with AR gene amplification more frequently (p=0.0342) shelv ed positive p53 immunostaining than tumours,without AR gene amplification, 75 and 27 percent, respectively. In summary, this study has shown that a ce ll clone with P53 mutation seems to be selected for during endocrine therap y and that positive p53 immunostaining correlates with AR gene amplificatio n. These results suggest that inactivation of P53 may lead to genetic insta bility in a subset of prostate carcinomas enabling them to achieve properti es, such as AR gene amplification, that allow them to grow in low levels of androgens and therefore cause tumour progression. Copyright (C) 1999 John Wiley & Sons, Ltd.