PTEN expression in non-small-cell lung cancer:: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration
PTEN expression in non-small-cell lung cancer:: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration
复制标题
DOI：
10.1016/j.humpath.2005.05.006
复制
发表时间：
2005-07-01
期刊：
影响因子：
3.3
通讯作者：
Kelsey, KT
中科院分区：
文献类型：
--
作者：
Marsit, CJ;Zheng, SC;Kelsey, KT
肿瘤抑制因子PTEN编码一种脂质磷酸酶，负调控磷脂酰肌醇3-激酶/AKT细胞存活通路。该基因的突变在脑癌、前列腺癌、子宫内膜癌和胃癌中很常见，但在非小细胞肺癌（NSCLC）中很少发生，尽管PTEN蛋白在肺肿瘤中经常丢失。我们在原发性NSCLC的外科病例系列研究中研究了PTEN启动子的高甲基化、染色体10q23微卫星（PTEN位点周围和基因内）杂合性缺失（LOH）、PTEN高度同源假基因PTENP1的高甲基化及其与PTEN蛋白缺失的关系。PTEN蛋白表达在74%（86/117）的肿瘤中降低或缺失，在中度分化的肿瘤中更常见。在鳞状细胞癌中，PTEN丢失在早期（I期或II期）疾病中更为常见。PTEN蛋白丢失在TP53染色低或无异常的肿瘤中也更常见。PTEN甲基化发生在26%（39/151）的肿瘤中，而10q23位点的LOH很少见，仅发生在19%（17/90）的信息肿瘤中。甲基化和LOH都不是PTEN蛋白表达的显著预测因子，尽管LOH只发生在早期疾病。在非小细胞肺癌中，PTEN蛋白表达的缺失经常发生，尽管导致PTEN蛋白表达缺失的机制尚不清楚是由于缺失还是表观遗传沉默。PTEN缺失也可能是一个有利的预后标志，尽管需要进一步的研究来证实这一发现。(C) 2005爱思唯尔公司版权所有。
The tumor suppressor PTEN encodes a lipid phosphatase that negatively regulates the phosphatidylinositol 3-kinase/AKT cell survival pathway. Mutations of this gene are common in brain, prostate, endometrial, and gastric cancers but occur rarely in non-small-cell lung cancer (NSCLC), although the PTEN protein is often lost in lung tumors. We have studied hypermethylation of the PTEN promoter, loss of heterozygosity (LOH) at microsatellites in chromosome 10q23 (surrounding and intragenic to the PTEN locus), and hypermethylation of PTEN's highly homologous pseudogene, PTENP1, and their association with PTEN protein loss in a surgical case series study of primary NSCLC. PTEN protein expression was reduced or lost in 74% (86/117) of tumors, with loss occurring more often in well to moderately differentiated tumors. In squamous cell carcinomas, PTEN loss occurred significantly more often in early-stage (stage I or II) disease. PTEN protein loss also occurred more frequently in tumors with low to no aberrant TP53 staining. Methylation of PTEN occurred in 26% (39/151) of tumors, and LOH at 10q23 was rare, occurring in only 19% (17/90) of informative tumors. Neither methylation nor LOH was a significant predictor of PTEN protein expression, although LOH occurred exclusively in early-stage disease. In NSCLC, loss of PTEN protein expression occurs frequently, although the mechanism responsible for loss is not clearly attributable to deletion or epigenetic silencing. PTEN loss may also be a favorable prognostic marker, although further studies are needed to confirm this finding. (C) 2005 Elsevier Inc. All rights reserved.