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GSTP1 启动子 CpG 岛甲基化在根治性前列腺切除术后手术切缘隐匿性肿瘤细胞 DNA 检测中的应用。

GSTP1 CpG island hypermethylation for DNA-based detection of occult tumor cells in surgical margins after radical prostatectomy.

机构信息

Department of Urology, University Hospital Ulm, Prittwitzstrasse 43, Ulm, Germany.

出版信息

World J Urol. 2012 Aug;30(4):541-6. doi: 10.1007/s00345-011-0764-2. Epub 2011 Sep 24.

DOI:10.1007/s00345-011-0764-2
PMID:21947551
Abstract

OBJECTIVE

The risk of local recurrence after radical prostatectomy (RP) is considerably dependent on local tumor stage. To improve local staging, the aim of this study was to assess the feasibility of quantitative methylation-specific PCR (Q-MSP) for the identification of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) to detect occult prostate cancer (PCa) cells in the prostatic fossa after RP.

METHODS

A total of 39 consecutive patients with clinically organ-confined PCa underwent RP. After gland excision, biopsies were obtained from eight defined areas of the prostatic fossa and bisected for both histopathological and molecular analyses. Results were related to clinicopathological data including tumor stage, Gleason score, prostate-specific antigen (PSA), and biochemical recurrence.

RESULTS

Of 39 patients, 11 with PCa had at least one positive molecular margin status indicated by GSTP1 methylation. These included 5 of 17 (29.4%) with organ-confined and 6 of 22 (27.3%) with advanced (≥pT3 and/or pN+) PCa. GSTP1 methylation in surgical margins strongly correlated with histopathological R-status (P = 0.022) and preoperative PSA (P = 0.01) whereas no association with tumor stage (pT2 vs pT3), grade (Gleason score <7 vs ≥7), and lymph node status was found. No patient experienced biochemical relapse.

CONCLUSIONS

GSTP1 hypermethylation detected by Q-MSP in prostatic fossa biopsies after RP is well suited for the detection of occult tumor cells in surgical margins. However, the limited number of patients and the short-term follow-up does not allow definite conclusions on the prognostic value of GSTP1 in surgical margins.

摘要

目的

根治性前列腺切除术(RP)后局部复发的风险在很大程度上取决于局部肿瘤分期。为了改善局部分期,本研究旨在评估定量甲基化特异性 PCR(Q-MSP)识别解毒谷胱甘肽-S-转移酶 P1 基因(GSTP1)启动子超甲基化以检测 RP 后前列腺窝隐匿性前列腺癌(PCa)细胞的可行性。

方法

39 例临床局限性 PCa 患者连续接受 RP。腺体切除后,从前列腺窝的 8 个定义区域获取活检,并进行组织病理学和分子分析的半切。结果与临床病理数据相关,包括肿瘤分期、Gleason 评分、前列腺特异性抗原(PSA)和生化复发。

结果

39 例患者中,11 例至少有一个阳性分子边缘状态,提示 GSTP1 甲基化。这些患者包括 17 例器官受限患者中的 5 例(29.4%)和 22 例进展期(≥pT3 和/或 pN+)PCa 患者中的 6 例。手术边缘的 GSTP1 甲基化与组织学 R 状态(P=0.022)和术前 PSA(P=0.01)强烈相关,而与肿瘤分期(pT2 与 pT3)、分级(Gleason 评分<7 与≥7)和淋巴结状态无关。没有患者发生生化复发。

结论

RP 后前列腺窝活检中通过 Q-MSP 检测到的 GSTP1 高甲基化非常适合检测手术边缘隐匿性肿瘤细胞。然而,患者数量有限且随访时间短,无法确定 GSTP1 在手术边缘的预后价值。

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本文引用的文献

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Gene promoter methylation in prostate tumor-associated stromal cells.
前列腺癌肿瘤旁非肿瘤组织中 APC 和 GSTP1 的甲基化与前列腺癌死亡率。
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Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911).前列腺癌根治术后的术后放疗:一项随机对照试验(欧洲癌症研究与治疗组织试验22911)
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Clin Cancer Res. 2005 Jun 1;11(11):4037-43. doi: 10.1158/1078-0432.CCR-04-2446.
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Molecular biomarker in prostate cancer: the role of CpG island hypermethylation.前列腺癌中的分子生物标志物:CpG岛高甲基化的作用。
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