Jerónimo Carmen, Usadel Henning, Henrique Rui, Silva Cristina, Oliveira Jorge, Lopes Carlos, Sidransky David
Department of Otolaryngology, Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Urology. 2002 Dec;60(6):1131-5. doi: 10.1016/s0090-4295(02)01949-0.
To further determine the value of real-time quantitative methylation-specific polymerase chain reaction (MSP) of GSTP1 as a molecular tool for the detection of prostate adenocarcinoma. Recent studies have shown a high frequency (more than 90%) of GSTP1 gene promotor methylation in prostate adenocarcinoma and a lower frequency in DNA from serum and urine.
Tissue samples from 69 patients with early-stage prostate adenocarcinoma and 31 patients with benign prostatic hyperplasia were collected. Matched urine and plasma specimens were obtained preoperatively. After sodium-bisulfite treatment, extracted DNA was analyzed for GSTP1 promoter hypermethylation both by conventional and real-time quantitative MSP.
In tissue samples, GSTP1 hypermethylation was detected in 63 (91.3%) of the 69 patients with cancer and in 9 (29%) of the 31 patients with benign prostatic hyperplasia. Conventional MSP detected GSTP1 hypermethylation in a larger number of urine and plasma samples than did real-time quantitative MSP (53.6% versus 31.9%, overall). In all positive bodily fluids, the paired tumor was also confirmed to be methylated. GSTP1 hypermethylation was detected by both MSP methods in only one urine sample (3.2%) from a patient with benign prostatic hyperplasia.
Although not quantitative, conventional MSP is currently more sensitive than real-time quantitative MSP in the detection of GSTP1 hypermethylation in bodily fluids from patients with prostate cancer with clinically localized disease. The value of quantitative determinations in monitoring and risk assessment remains to be further explored.
进一步确定谷胱甘肽S-转移酶P1（GSTP1）实时定量甲基化特异性聚合酶链反应（MSP）作为检测前列腺腺癌分子工具的价值。近期研究表明，前列腺腺癌中GSTP1基因启动子甲基化频率较高（超过90%），而血清和尿液DNA中的频率较低。
收集69例早期前列腺腺癌患者和31例良性前列腺增生患者的组织样本。术前获取配对的尿液和血浆标本。经亚硫酸氢钠处理后，采用传统和实时定量MSP分析提取的DNA中GSTP1启动子的高甲基化情况。
在组织样本中，69例癌症患者中有63例（91.3%）检测到GSTP1高甲基化，31例良性前列腺增生患者中有9例（29%）检测到。传统MSP检测到的尿液和血浆样本中GSTP1高甲基化数量多于实时定量MSP（总体为53.6%对31.9%）。在所有阳性体液中，配对肿瘤也被证实发生甲基化。仅在1例良性前列腺增生患者的尿液样本（3.2%）中，两种MSP方法均检测到GSTP1高甲基化。
虽然不是定量检测，但在检测临床局限性前列腺癌患者体液中GSTP1高甲基化方面，传统MSP目前比实时定量MSP更敏感。定量测定在监测和风险评估中的价值仍有待进一步探索。
