摘要
目的:探讨子宫内膜癌中DNA甲基转移酶3B(DNA methyltransferase 3B,DNMT3B)的表达特点、与雌激素受体(estrogen receptor,ER)和孕激素受体(progesterone receptor,PR)的相关性及意义。方法:免疫组织化学法检测DNMT3B、ER、PR在104例子宫内膜癌组织中的表达并与临床病理特点及预后相对照。结果:104例子宫内膜癌组织中DNMT3B阳性率为50%,Ⅰ型内膜癌(内膜样癌)中DNMT3B过表达率(54.8%)显著高于Ⅱ型内膜癌(30.0%,P=0.028),且Ⅰ型内膜癌中,随肿瘤分化变差,DNMT3B阳性率增加(1级、2级、3级分别为43.3%、51.3%、86.7%),差异有统计学意义(P=0.019)。DNMT3B在肌层侵犯程度重、存在脉管癌栓、淋巴结转移及分期晚的病例中过表达率更高,DNMT3B过表达的患者组预后更差,但差异未见统计学意义(P>0.05)。Ⅰ型内膜癌DNMT3B与ER、PR表达呈负相关,ER、PR阴性组DNMT3B过表达率(78.9%、86.7%)高于ER、PR阳性组DNMT3B过表达率(47.7%、47.8%),差异有统计学意义(P=0.016,P=0.006);ER、PR均阴性时,DNMT3B过表达率最高(92.9%),差异有统计学意义(P=0.002)。Ⅱ型内膜癌中DNMT3B与ER、PR表达未见相关性(P>0.05)。序列分析显示,DNMT3B基因启动子区有多个ER、PR结合位点。结论:内膜样癌与非内膜样癌中DNMT3B表达特点不同,DNMT3B过表达有可能作为预后或预测因子而辅助病理诊断和生物学行为评估。Ⅰ/Ⅱ型子宫内膜癌的甲基化特点可能不同,Ⅰ型内膜癌中DNMT3B过表达与ER、PR表达呈负相关,Ⅱ型内膜癌中DNMT3B表达与ER、PR表达关系不大。
Objective： To determine the clinicopathological significance of the DNA methyltransferase3B（ DNMT3B） overexpression in endometrial carcinomas and to evaluate its correlation with hormone receptor status. Methods： Immunohistochemistry was performed to assess the expression of DNMT3 B and hormone receptors in 104 endometrial carcinomas. Results： DNMT3 B overexpression occurred frequently in endometrioid carcinoma（ EC,54. 8%） more than in nonendometrioid carcinoma（ NEC,30. 0%）with statistical significance（ P = 0. 028）. Furthermore,there was a trend that EC with worse clinicopathological variables and shorter survival had a higher DNMT3 B expression,and the correlation between DNMT3 B and tumor grade reached statistical significance（ P = 0. 019）. A negative correlation between DNMT3 B and estrogen receptor（ ER） or progesterone receptor（ PR） expression was found in EC.NMT3 B overexpression occurred frequently in the ER or PR negative subgroups（ 78. 9%,86. 7%） more than in the positive subgroups（ 47. 7%,47. 8%） with statistical significance（ P = 0. 016,P = 0. 006）.In addition,the DNMT3 B overexpression increased in tumors with both ER and PR negative expression（ 92. 9%,P = 0. 002）. However,no such correlation was found in NEC（ P〉0. 05）. Sequence analyses demonstrated multiple ER and PR binding sites in the promoter regions of DNMT3 B gene. Conclusion：This study showed that the expression of DNMT3 B in EC and NEC was different. DNMT3 B overexpression in EC was associated with the worse clinicopathological variables and might have predictive value.The methylation status of EC and NEC maybe different. In addition,in EC,DNMT3 B overexpression negatively correlated with ER or PR expression. In NEC,the correlation between DNMT3 B and ER or PR status was not present.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2016年第5期788-794,共7页
Journal of Peking University:Health Sciences
基金
新疆维吾尔自治区自然科学基金(201318101-2)资助~~
