Alpha-methylacyl-CoA racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): Association with diagnosis of prostate cancer

Alpha-methylacyl-CoA racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): Association with diagnosis of prostate cancer
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DOI:
10.1002/pros.20196
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发表时间:
2005-06-01
期刊:
影响因子:
2.8
通讯作者:
Gann, PH
Gann, PH
中科院分区:
医学3区
文献类型:
--
作者:
Ananthanarayanan, V;Deaton, RJ;Gann, PH

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背景α-甲酰基-CoA消旋酶(AMACR)在前列腺癌中强表达,在高级别前列腺上皮内瘤变(HGPIN)中表达可变,在正常前列腺中表达低。我们研究了HGPLN和正常组织中AMACR的表达是否与随后的癌症诊断或癌灶附近相关。对45例单纯HGPIN患者、12例前列腺癌根治术(RP)标本和6例非前列腺癌膀胱切除术标本进行AMACR免疫组化染色。在HGPIN患者中,23例(病例)在随后的活检中显示癌症,22例(对照)没有癌症,至少连续3次活检阴性。在活检组中,病例正常区室中每个腺体的平均AMACR表达(0.29)显著高于对照组(0.21)(P=0.0006)。在RP组中,癌灶附近的正常腺体的平均AMACR表达高于远处的正常腺体(P=0.0006)。在活检中,病例和对照组之间的HGPIN区室或RP组的近端和远端腺体之间没有差异。膀胱癌切除术标本中正常腺体的平均AMACR染色显著低于癌灶附近的正常腺体。AMACR在癌灶附近的正常腺体中以及最终显示癌症的受试者中的较高表达表明前列腺癌发生中可能存在场效应。因此,正常腺体中AMACR的表达可能是重复活检结果的有用预测因子,或作为化学预防研究的中间终点。(c)2004 Wiley-Liss,Inc.
BACKGROUND. Alpha-methylacyl-CoA racemase (AMACR) is strongly expressed in prostate cancer with variable expression in high-grade prostatic intraepithelial neoplasia (HGPIN) and low expression in normal prostate. We examined whether AMACR expression in HGPLN and normal tissue was associated with subsequent diagnosis of cancer or proximity to a cancer focus.METHODS. Needle core biopsies from 45 patients with isolated HGPIN, 12 radical prostatectomy (RP) specimens with prostatic carcinoma and 6 cystoprostatectomies without prostatic carcinoma were immunostained for AMACR. Among patients with HGPIN, 23 (cases) showed cancer on a later biopsy and 22 (controls) had no cancer with at least 3 consecutive negative biopsies.RESULTS. In the biopsy set, the mean AMACR expression per gland in the normal compartment of the cases (0.29) was significantly higher than the controls (0.21) (P=0.0006). In the RP set, normal glands near a cancer focus had higher mean AMACR expression than those that were distant (P=0.0006). There was no difference within the HGPIN compartment between cases and controls in the biopsies, or between near and distant glands in the RP set. Mean AMACR staining of normal glands in the cystoprostatectomy specimens was significantly lower than in normal glands in close proximity to a cancer focus.CONCLUSIONS. Higher expression of AMACR in normal glands near a focus of cancer, as well as in the subjects eventually showing cancer, suggests a possible field effect in prostatic carcinogenesis. AMACR expression in normal glands therefore might be a useful predictor for repeat biopsy outcomes or as an intermediate endpoint in chemoprevention studies. (c) 2004 Wiley-Liss, Inc.