Ho Chih-Ming, Lin Ming-Chieh, Huang Shih-Hung, Huang Chi-Jung, Lai Hung-Cheng, Chien Tsai-Yen, Chang Shwu-Fen
Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan.
Gynecol Oncol. 2009 Feb;112(2):307-13. doi: 10.1016/j.ygyno.2008.09.040. Epub 2008 Nov 12.
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.
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 markers.
Of the 40 OCCAs, 37.5% (15/40) had reduced PTEN immunoreactivity, LOH was found in 33% (6/18) of OCCAs, and 31% (4/13) 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.
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.
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PTEN突变并不常见。OCCA中PTEN基因沉默的机制仍不清楚。
对40例OCCA石蜡包埋组织进行PTEN表达的免疫组织化学分析。通过甲基化特异性PCR检测24例OCCA组织和5株OCCA细胞系中PTEN启动子甲基化情况。使用5个多态性标记对18例OCCA患者和13例浆液性腺癌进行10q23杂合性缺失（LOH）分析。
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%（4/13）的浆液性腺癌中发现了LOH。在33%存在LOH的OCCA中，只有33%（2/6）的PTEN表达缺失。通过甲基化特异性PCR检测，5株OCCA细胞系和24例OCCA组织中PTEN启动子未甲基化。未发现PTEN表达与疾病晚期或总生存期之间存在显著相关性。
我们的结果表明，超过三分之一的OCCA病例检测到PTEN表达降低。PTEN启动子甲基化和10q23位点的LOH均与PTEN失活无显著相关性，且不是OCCA的不良预后因素。
