Gonzalgo Mark L, Pavlovich Christian P, Lee Shing M, Nelson William G
The James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-2101, USA.
Clin Cancer Res. 2003 Jul;9(7):2673-7.
We assess the feasibility of a urinary test for prostate cancer detection in a high-risk patient cohort based on methylation-specific PCR analysis of the pi class glutathione S-transferase (GSTP1) gene promoter.
A total of 45 men underwent transrectal ultrasound-guided biopsy of the prostate for suspected malignancy. Clean-catch voided urine specimens were prospectively collected from each patient immediately after biopsy. Genomic DNA was isolated from urine specimens and subjected to sodium bisulfite modification. Methylation of the GSTP1 promoter was examined in a blinded manner by methylation-specific PCR analysis and correlated with pathology results, and clinical information was obtained from the patient record.
Methylation of GSTP1 in the urine was detected in a total of 18 of 36 (50%) informative cases. A total of 7 of 18 (39%) patients with prostate adenocarcinoma identified on their initial biopsy had detectable urinary GSTP1 methylation (58% sensitivity among informative cases). Abnormal urinary GSTP1 methylation was also detected in 7 of 21 (33%) patients without evidence of cancer on biopsy and in 4 of 6 (67%) patients diagnosed with atypia or high-grade prostatic intraepithelial neoplasia.
We have demonstrated the feasibility of a novel, noninvasive molecular approach for the detection of epigenetic changes associated with prostate cancer. A screening test based on GSTP1 methylation in the urine specimens of patients with suspected prostate malignancy may be a useful adjunct to serum screening tests and digital rectal examination findings for identification of men at increased risk of harboring cancer despite a negative biopsy. This molecular assay has potential application for stratification of patients into low- and high-risk groups for surveillance versus repeat biopsy.
基于pi类谷胱甘肽S-转移酶（GSTP1）基因启动子的甲基化特异性PCR分析，我们评估在高危患者队列中进行前列腺癌检测尿液检测的可行性。
共有45名男性因疑似恶性肿瘤接受经直肠超声引导下前列腺活检。活检后立即前瞻性地从每位患者收集清洁中段尿标本。从尿标本中分离基因组DNA并进行亚硫酸氢钠修饰。通过甲基化特异性PCR分析以盲法检测GSTP1启动子的甲基化，并与病理结果相关联，且从患者记录中获取临床信息。
在36例信息充分的病例中，共有18例（50%）检测到尿液中GSTP1甲基化。在初次活检时确诊为前列腺腺癌的18例患者中，共有7例（39%）检测到尿液GSTP1甲基化（信息充分病例中的敏感性为58%）。在21例活检无癌症证据的患者中，有7例（33%）也检测到尿液GSTP1甲基化异常，在6例诊断为异型增生或高级别前列腺上皮内瘤变的患者中，有4例（67%）检测到异常。
我们已经证明了一种用于检测与前列腺癌相关的表观遗传变化的新型非侵入性分子方法的可行性。基于疑似前列腺恶性肿瘤患者尿液标本中GSTP1甲基化的筛查试验，对于血清筛查试验和直肠指检结果而言，可能是一种有用的辅助手段，用于识别尽管活检结果为阴性但患癌风险增加的男性。这种分子检测方法在将患者分层为低风险和高风险组以进行监测或重复活检方面具有潜在应用价值。
