Expression and somatic mutation on androgen receptor gene in prostate cancer.
BACKGROUND
Lack of androgen receptor (AR) expression or mutation on the AR gene creates the tendency for androgen independence and progression of prostate cancer. However, the association between the progression and AR expression or mutations is still controversial. In this study, we evaluated the prognostic significance of AR expression and mutations in prostate cancers.


METHODS
Forty-two prostate adenocarcinomas and three lymph node metastatic lesions sampled prior to hormonal therapy were included in this study; AR expression was analyzed immunohistochemically using an antibody against AR and the result was scored as the percentage of AR-positive tumor cells in the total tumor cells. Polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing were used to detect AR mutations.


RESULTS
Our study revealed the average AR expression in the prostate adenocarcinoma was 52.2 +/- 27.1%, which was significantly lower than that in the adjacent non-tumorous prostate tissue (68.3 +/- 18.3% in average) (P < 0.001). A significant correlation was obtained between progression-free survival and AR expression (P < 0.01). By SSCP analysis, three silent mutations (T649T, E709E and E711E) were detected in three separate prostate carcinomas.


CONCLUSIONS
: We conclude that AR expression is a useful prognostic indicator for tumor progression. Androgen receptor mutation may be an uncommon molecular event in untreated prostate cancer in Japanese men.
Segawa
Naoki
N
Department of Urology, Osaka Medical College, Osaka, Japan. uro009@poh.osaka-med.ac.jp
Nakamura
Misa
M
Shan
Liang
L
Utsunomiya
Hirotoshi
H
Nakamura
Yasushi
Y
Mori
Icihiro
I
Katsuoka
Yoji
Y
Kakudo
Kennichi
K
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
D011944:Receptors, Androgen