Woodson Karen, O'Reilly Keith J, Hanson Jeffrey C, Nelson Dayne, Walk Elyse L, Tangrea Joseph A
Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
J Urol. 2008 Feb;179(2):508-11; discussion 511-2. doi: 10.1016/j.juro.2007.09.073.
Prostate cancer has a unique set of problems associated with its early detection and diagnosis that might be aided by the addition of molecular markers, such as DNA hypermethylation. DNA methylation is an important epigenetic mechanism of gene regulation that has a critical role in normal developmental processes. Aberrant DNA methylation is a hallmark of carcinogenesis and GSTP1 hypermethylation is the most common molecular alteration in human prostate cancer. To our knowledge the clinical usefulness of the detection of gene methylation is yet to be established.
We evaluated GSTP1 hypermethylation in urine collected after prostatic massage and in core needle biopsies from 100 men referred for diagnostic biopsy.
Methylation of GSTP1 in urine specimens had 75% sensitivity and 98% specificity for prostate cancer. GSTP1 methylation in the biopsy had 88% specificity and 91% sensitivity. Interestingly we observed a higher frequency of GSTP1 methylation in the urine of men with stage III vs II disease (100% vs 20%, p = 0.05).
This study suggests that the detection of GSTP1 methylation in prediagnostic urine may improve the specificity of PSA and help distinguish men with prostate cancer from those with benign prostatic hyperplasia. This finding should be further explored in a larger, prospective screening trial.
前列腺癌在早期检测和诊断方面存在一系列独特问题，添加分子标志物（如DNA高甲基化）可能有助于解决这些问题。DNA甲基化是一种重要的基因调控表观遗传机制，在正常发育过程中起关键作用。异常DNA甲基化是致癌作用的标志，而GSTP1高甲基化是人类前列腺癌中最常见的分子改变。据我们所知，基因甲基化检测的临床实用性尚未确立。
我们评估了100名因诊断性活检前来就诊的男性患者经前列腺按摩后收集的尿液以及芯针活检组织中GSTP1的高甲基化情况。
尿液标本中GSTP1甲基化对前列腺癌的敏感性为75%，特异性为98%。活检组织中GSTP1甲基化的特异性为88%，敏感性为91%。有趣的是，我们观察到III期疾病男性尿液中GSTP1甲基化的频率高于II期疾病男性（分别为100%和20%，p = 0.05）。
本研究表明，在诊断前尿液中检测GSTP1甲基化可能提高前列腺特异性抗原（PSA）的特异性，并有助于区分前列腺癌患者与良性前列腺增生患者。这一发现应在更大规模的前瞻性筛查试验中进一步探索。
