PTEN、MMP-7在子宫内膜增殖症及Ⅰ型子宫内膜癌中的表达及意义

The expression of PTEN,MMP-7 in endometrial hyperplasia and type Ⅰ endometrial adenocarcinoma

目的:分析基质金属蛋白酶-7(MMP-7)和抑癌基因(PTEN)在子宫内膜增殖症与Ⅰ型内膜癌组织中的异常表达及变化规律,探讨其作为子宫内膜早期癌变及浸润、转移的生物学标志的可能性。方法:应用免疫组化Envision法对30例正常增生期子宫内膜组织、80例子宫内膜增殖症组织、76例Ⅰ型子宫内膜癌组织中MMP-7、PTEN蛋白的表达进行检测。结果:在正常增生期子宫内膜、子宫内膜简单型增生、复杂型增生、非典型增生、Ⅰ型内膜癌(包括浸润深度<1/2肌层、≥1/2肌层)MMP-7蛋白的阳性表达率呈递增趋势,PTEN则呈递减趋势。等级相关分析结果显示,MMP-7、PTEN表达异常与癌组织学分级均显著相关(相关系数r分别为0.410、-0.569,P值均<0.01)。除非典型增生外,正常增生期子宫内膜、子宫内膜简单型增生、复杂型增生与Ⅰ型内膜癌组织中的MMP-7、PTEN蛋白表达差异有统计学意义;正常增生期子宫内膜、子宫内膜简单型增生与非典型增生比较,MMP-7、PTEN蛋白表达差异有统计学意义;在Ⅰ型内膜癌中,MMP-7、PTEN表达存在负相关性(r=-0.392,P<0.01);MMP-7与肿瘤浸润深度呈正相关(r=0.389,P<0.05);PTEN蛋白表达与Ⅰ型内膜癌的手术分期、组织学分级无关(P>0.05),与肌层浸润呈负相关(P<0.05)。结论:MMP-7、PTEN蛋白在子宫内膜增殖症至Ⅰ型内膜癌组织中表达异常,MMP-7的高表达与肿瘤浸润深度有关,PTEN基因异常表达与子宫内膜的早期癌变关系密切,两者可能成为子宫内膜组织早期癌变和预测生物学行为的重要分子标志物。

Objective：To study the abnormal expression and varing regulations of PTEN and MMP-7 in endometrial hyperplasia and type Ⅰ endometrial adenocarcinoma,and to investigate the possibilities of them as biomarkers of early carcinogenesis of endometria,transfer and infiltration of endometrial cancer.Methods：The expressions of PTEN and MMP-7 in 30 normal proliferative endometria,80 endometrial typerplasia and 76 endometrial adenocarcinoma were detected by immunohistochemical staining En vision method.Results：The positive expression rates of MMP-7 increased gradually and those of PTEN decreased gradually in normal proliferative endometria,endometria of simple proliferation,endometria of complicated proliferation,endometria of atypical proliferation and type Ⅰendometrial adenocarcinoma （including infiltrative depth less than 1 /2 of muscle lager and more than 1 /2 of muscle lager）.The results of grade correlation analysis indicated that the abnormal expressions of MMP-7 and PTEN were well both correlated with the pathological grading of adenocarcinoma （r=0.410,-0.532,P 0.01）.Except for atypical proliferation,normal proliferative endometria,endometria of simple proliferateion,endometria of complicated proliferation,were markedly different with and those of endometrial adenocarcinoma.The expression of MMP-7 and PTEN in normal proliferateive endometria and endometria of atypical proferation of MMP-7 and PTEN in type Ⅰendometrial adenocarcinoma （r=-0.392,P 0.01）.There were positive correlation between MMP-7 and the depth of infiltration of endometrial adenocarcinoma （r =0.389,P 0.05）.No correlation was found between the expression of PTEN and operation grading,histological grading （P 0.05）,while negatively correlated with myometrial invasion （P 0.05）.Conclusion：The expressions of MMP-7 and PTEN are abnormal in endometrial hyperplasia to type Ⅰendometrial adenocarcinoma.The high expression of MMP-7 is closely associated with the depth of infiltration of endometrial adenocarcinoma.The abnormal expression of PTEN is closely associated with early carcinogenesis of endometrial and they may become important biomarkers of early carcinogenesis of endometria and predicting biological actions.