Androgen receptor gene amplification and protein expression in recurrent prostate cancer

Androgen receptor gene amplification and protein expression in recurrent prostate cancer
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DOI:
10.1097/01.ju.0000091873.09677.f4
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发表时间:
2003-11-01
期刊:
影响因子:
6.6
通讯作者:
Mohler, JL
Mohler, JL
中科院分区:
医学1区
文献类型:
--
作者:
Ford, OH;Gregory, CW;Mohler, JL

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目的:雄激素受体(AR)在雄激素依赖性和复发性前列腺癌中高度表达,表明其在雄激素剥夺后的肿瘤生长和进展中发挥作用。AR扩增可能有助于雄激素受体的激活,在相对雄激素absence.Materials和方法:福尔马林固定和冷冻标本的复发性前列腺癌,获得经尿道切除术的前列腺特异性抗原的血清水平增加,其中尿潴留的男性。AR扩增和X染色体数目通过双色荧光原位杂交测定,AR蛋白表达通过自动图像分析测定。我们比较了复发性前列腺癌患者的临床特征和生存率,其肿瘤有或没有表现出AR扩增和X染色体polysomy.Results:33%的24例复发性前列腺癌标本8(33%)显示AR扩增。AR在扩增(AMP)AR的肿瘤中(平均光密度0.36 +/- 0.07)比在缺乏扩增(NO AMP)的肿瘤中(平均光密度0.24 +/- 0.09)更强的免疫染色。两组血清前列腺特异性抗原水平比较无差异(AMP 11.9,14.8; NO AMP 26.0,60.3),格里森总和(AMP 9.0,0.5; NO AMP 9.0,1.0),临床TNM分期(AMP 4例MO,M1 4; NO AMP 8例MO,8例M1),种族(AMP 6例白色和2例黑人,NO AMP白色和7例黑人)或生存月数(AMP 47.5,28.5; NO AMP 33.5,72.0)。三个复发性前列腺癌标本(13%)表现出X染色体拷贝数2或更大,并没有发现差异时,比较这些groups.Conclusions的临床特征:AR扩增在复发性前列腺癌的结果在更高水平的AR蛋白表达,但不影响生存。
Purpose: The androgen receptor (AR) is highly expressed in androgen dependent and recurrent prostate cancer, suggesting that it has a role in tumor growth and progression after androgen deprivation. AR amplification may contribute to androgen receptor activation in relative androgen absence.Materials and Methods: Formalin fixed and frozen specimens of recurrent prostate cancer were obtained by transurethral resection from men with increasing serum level of prostate specific antigen in whom urinary retention developed. AR amplification and X-chromosome number were determined by 2-color fluorescence in situ hybridization, and AR protein expression was determined by automated image analysis. We compared clinical characteristics and survival of patients with recurrent prostate cancer whose tumors did or did not exhibit AR amplification and X-chromosome polysomy.Results: Thirty-three percent of the 24 recurrent prostate cancer specimens 8 (33%) showed AR amplification. AR was more intensely immunostained in tumors with amplified (AMP) AR (mean optical density 0.36 +/- 0.07) than in tumors lacking amplification (NO AMP) (mean optical density 0.24 +/- 0.09). No differences were found between the 2 groups when comparing serum levels of prostate specific antigen (AMP 11.9, 14.8; NO AMP 26.0, 60.3), Gleason sum (AMP 9.0, 0.5; NO AMP 9.0, 1.0), clinical TNM stage (AMP 4 cases MO, M1 4; NO AMP 8 MO, 8 M1), race (AMP 6 white and 2 black men, NO AMP white and 7 black men) or survival in months (AMP 47.5, 28.5; NO AMP 33.5, 72.0). Three of the recurrent prostate cancer specimens (13%) demonstrated X-chromosome copy number 2 or greater and no differences were found when comparing clinical characteristics between these groups.Conclusions: AR amplification in recurrent prostate cancer results in higher levels of AR protein expression but does not affect survival.