PTEN promoter methylation and LOH of 10q22-23 locus in PTEN expression of ovarian clear cell adenocarcinomas

PTEN promoter methylation and LOH of 10q22-23 locus in PTEN expression of ovarian clear cell adenocarcinomas
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DOI:
10.1016/j.ygyno.2008.09.040
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发表时间:
2009-02-01
影响因子:
4.7
通讯作者:
Chang, Shwu-Fen
Chang, Shwu-Fen
中科院分区:
医学2区
文献类型:
--
作者:
Ho, Chih-Ming;Lin, Ming-Chieh;Chang, Shwu-Fen

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目标。磷酸酶和张力蛋白同源物 (PTEN) 表达缺失在卵巢透明细胞腺癌 (OCCA) 中很常见,但在 OCCA 中并不常见观察到 PTEN 突变。 OCCA中PTEN基因沉默的机制尚不清楚。材料与方法。在 40 个 OCCA 石蜡包埋的组织中进行 PTEN 表达的免疫组织化学分析。通过甲基化特异性 PCR 检查 24 种 OCCA 组织和 5 种 OCCA 细胞系中的 PTEN 启动子甲基化。对 18 名 OCCA 患者和 13 名浆液性腺癌患者进行了 10q23 杂合性丢失 (LOH) 分析,其中有 5 个多态性市场。结果。在 40 例 OCCA 中,37.5% (15/40) 的 PTEN 免疫反应性降低,33% (6/18) 的 OCCA 和 31% (4113) 的浆液性腺癌中发现 LOH。在 33% 患有 LOH 的 OCCA 中,只有 33% (2/6) 丢失了 PTEN 表达。 MSP-PCR检测5个OCCA细胞系和24个OCCA组织中PTEN启动子未甲基化。没有发现PTEN表达与晚期疾病或总生存期之间存在显着相关性。结论。我们的结果表明,在超过三分之一的 OCCA 病例中检测到 PTEN 表达减少。 PTEN 启动子甲基化和 10q23 位点的 LOH 均与 PTEN 失活显着相关,并且不是 OCCA 的不良预后因素。 (C) 2008 Elsevier Inc. 保留所有权利。
Objectives. Loss of phosphatase and tensin homolog (PTEN) expression is common in ovarian clear cell adenocarcinomas (OCCA), but PTEN mutations are not frequently observed in OCCA. The mechanism of PTEN gene silencing in OCCA is still not clear.Materials and methods. Immunohistochemical analysis of PTEN expression was performed in 40 OCCA paraffin-embedded tissues. PTEN promoter methylation in 24 OCCA tissues and 5 OCCA cell lines was examined by methylation-specific PCR. Eighteen OCCA patients and 13 serous adenocarcinomas were analyzed for loss of heterozygosity (LOH) at 10q23 with five polymorphic markets.Results. Of the 40 OCCAs, 37.5% (15/40) had reduced PTEN immunoreactivity, LOH was found in 33% (6/18) of OCCAs, and 31% (4113) of serous adenocarcinomas. In the 33% of OCCAs with LOH, only 33% (2/6) lost PTEN expression. PTEN promoter was unmethylated in 5 OCCA cell lines and 24 OCCA tissues detected by MSP-PCR. No significant correlation between PTEN expression and advanced stage disease or overall survival was found.Conclusion. Our results indicate that reduced PTEN expression was detected in more than one third of OCCA cases. Neither PTEN promoter methylation nor LOH at 10q23 locus is significantly related to PTEN inactivation and is not an adverse prognostic factor in OCCA. (C) 2008 Elsevier Inc. All rights reserved.