Epigenetic and genetic alternation of PTEN in cervical neoplasm
Epigenetic and genetic alternation of PTEN in cervical neoplasm
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DOI：
10.1016/j.ygyno.2004.03.013
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发表时间：
2004-06-01
影响因子：
4.7
通讯作者：
Wong, YF
中科院分区：
文献类型：
--
作者：
Cheung, TH;Lo, KWK;Wong, YF
目标。我们研究了PTEN的表观遗传和遗传改变在宫颈鳞状细胞癌（SCC）发生中的作用及其作为预后因素的价值。10例高级别宫颈上皮内瘤变（CIN-H）和62例SCC组织用于本研究。在通过启动子CpG岛甲基化导致PTEN功能丧失之前进行显微解剖，研究了缺失和突变。PTEN蛋白表达与临床病理信息一致。通过单链构象多态性（PCR-SSCP）评估的PTEN突变在62例SCC中均未发现。杂合性缺失（LOH）仅见于8例SCC。在40%（4/10）的CIN-H和58%（36/62）的SCC标本中检测到PTEN启动子甲基化。PTEN蛋白表达的缺失与PTEN的甲基化有关。PTEN甲基化与患者年龄、肿瘤分级或分期无关。患有持续性疾病或死于疾病的患者的PTEN甲基化百分比明显高于无复发证据的患者。多因素Cox回归模型证实PTEN是控制年龄、病理分级和临床分期后总生存率和无病生存率的重要预测因子。PTEN甲基化和PTEN表达缺失是宫颈癌发展的早期事件，可能具有预后意义。(C) 2004爱思唯尔公司版权所有。
Objectives. We studied the role of epigenetic and genetic changes of PTEN in the development of squamous cell carcinoma (SCC) of the uterine cervix and their value as a prognostic factor.Methods. Ten high-grade cervical intraepithelial neoplasia (CIN-H) and 62 SCC tissues were used in this study. Microdissection was performed before loss of PTEN function through methylation of promoter CpG islands, deletion and mutation were studied. The findings were verified with PTEN protein expression and correlated with clinicopathologic information.Results. PTEN mutation assessed by single-strand conformation polymorphism (PCR-SSCP) was not noted in any of the 62 SCC. Loss of heterozygosity (LOH) was only seen in eight SCC. PTEN promoter methylation was detected in 40% (4/10) of CIN-H and 58% (36/62) of SCC specimens. Loss of PTEN protein expression was associated with methylation of PTEN. PTEN methylation was not related to patient age, tumor grade or stage. Patients with persistent disease or who died of disease had a significantly higher percentage of PTEN methylation than those without evidence of recurrence. Multivariate Cox regression models confirmed PTEN was an important significant predictor both for total and disease-free survival after controlling age, pathologic grade and clinical stage.Conclusions. PTEN methylation and loss of PTEN expression are early events in the development of cervical cancer and may have prognostic significance. (C) 2004 Elsevier Inc. All rights reserved.