【作者】 孟令新；

【导师】 章明放；

【作者基本信息】 天津医科大学 ， 病理学， 2005， 硕士

【摘要】 目的: 通过检测ER、PTEN、bcl-2、bax、PCNA及TUNEL在正常子宫内膜、子宫内膜增殖症(包括单纯性增生、复杂性增生和不典型增生)和子宫内膜样腺癌组织中的表达情况,探讨以下问题: (1)、ER、PTEN在子宫内膜样腺癌发生发展中表达的序惯性变化,ER与PTEN表达的相关性,ER、PTEN与子宫内膜样腺癌临床病理学特征之间的关系。 (2)、bcl-2、bax在不同类型子宫内膜中的表达,二者的相关性分析及与临床病理学特征之间的关系。 (3)、PCNA与凋亡(TUNEL)在不同类型子宫内膜中的表达,探讨它们与癌组织临床病理学特征之间的关系。 (4)、探讨各指标在子宫内膜样癌发生发展中所起的作用和可能的分子机制,为其临床病理诊断、判断预后和有针对性的治疗提供一定的理论依据。 方法: 正常子宫内膜共10例(增生期和分泌期各5例),子宫内膜增殖症60例(单纯性增生、复杂性增生和不典型增生各20例),子宫内膜样腺癌20例。采用免疫组织化学两步法检测不同类型子宫内膜组织中各指标的表达,采用SPSS11.5统计软件包进行数据处理,以P<0.05为有显著性差异。 结果: 1.ER主要分布于子宫内膜腺上皮细胞的胞核中。正常子宫内膜增生期>分泌期(P<0.01)。增殖症>正常宫内膜(P<0.05),而内膜样癌中ER的表达明显低于增殖症和正常宫内膜(P<0.05)。在增殖症中,单纯>复杂(P<0.05),更多还原

【Abstract】 Objective:To analyze the expression of ER、 PTEN、 bcl-2、 bax、 PCNA and TUNELin the gland epithelial cells of various endometriums,then to investigate the following questions:(1) Gradualistic changes of ER and PTEN expression in the development of EAC.The effects of estrogen on PTEN expression.The relationship between ER,PTEN expression and clinicopathological characters of EAC.(2) Detecting bcl-2 and bax expression in different endometriums,the relationship between them and clinicopathological parameters of EAC.(3) The expression of PCNA and TUNEL in various endometriums.To investigate the relationship between PCNA,TUNEL expression and clinicopathological characters of EAC.(4) With these results,we want to make clear the roles that every index plays in the pathogenesis and progression of EAC and its possible molecular mechanism.Another purpose is to put ours discovers into the clinicopathological diagnosis, therapy and prognosis.Methods:We apply immunohistochemistry technique to detect ER, PTEN, bcl-2,bax,PCNA and TUNEL expression in 10 NE(PE and SE, respect tively 5 cases),60 EH(SH,CH and AH,respectively 20 cases) and 20 EAC.A11 data were processed by SPSS version 11.5 analysis software. Results:1. In NE,ER expression in PE are higher than that in SE (P<0.01).ER expression are different in various endometriums,EH>NE>EAC (P<0.05).There are some differences among the ER expression of various histological types of EH.Those are:SH> CH> AH(P<0.05).ER expression are not correlated with ages, DMI and pathological stages(p>0.05), but ER expression are associated with HG:WDEA >MDEA >LDEA(P<0.05).2. PTEN are mostly located in the nucleus and plasm of gland epithelial cells of the endornetrium.The differences are not significant for the PTEN expression in PE and SE(p>0.05).PTEN expression are gradually decreased from NE,EH to EAQand the differences are significant(p<0.01).The differences are significant between AH/SH and AH/CH (p<0.01). As for SH and CH,the differences are not significant(p>0.05).Though[<50]>[=50],[=l/2] >[>l/2],the differences of PTEN expression are not significant in different ages types and DMI(p>0.05).With the differentiation becoming poor and the clinical stages elevating,PTEN expression are decreasing,those are: I>II>III~IV; WDEA>MDEA>LDEA;but the differences are not significant(p>0.05).3. AS for the correlation analysis,Our results shows no correlation betwween PTEN and ER expression in the epithelial cells of both AH and EAC(p>0.05).4. bcl-2 expression are higher in PE than SE,however,bax are higher in SE than PE.Statistics shows that bcl-2 have no negative correlation with bax.5. bcl-2 and bax become increasing from SH,CH to AH(P<0.05). bcl-2 and bax are higher in AH than SH and CH,and the differences are significant (respectively, P<0.01,P<0.05).6. In the EAC, bcl-2 expression have no significant differences among different ages groups and DMI(P>0.05).But bcl-2 expression are associated with the HG and clinical stages:WDEA<MDEA<LDEA (P<0.01).m~rV< II < I (respectively,p<0.01,p<0.05).As for bax,there are no significant differences in different ages groups and clinical stages(P>0.05).With the differentiation becoming poor and the myometrial invasion deeping,bax expression are decreasing,and its expression are associated with the HG and DMI:well>moderate>low(P<0.01); [>l/2] >[=l/2] (P<0.01).There are positivecorrelations between expression of bcl-2 and bax in EAC(rs= 0.997,p<0.01).7. PCNA expression are increasing from NE,EH to EAC.Those are: EAC>AH>CH>SH>NE(P<0.05).In the EAC,PCNA expression are associatedwith DMI,HG and clinical stages.Those are: [>l/2]>[=l/2], LDEA>MDEA>WDEA,III> I ,III> II ,and with the myometrial invasion deeping,differentiation becoming poor and the clinical stages elevating,PCNA expression are increasing.Though PCNA expression of the [=50] ages group are higher than the [<50] group,the differences are not significant(p>0.05).8. We have only found some dispersed apoptostic cells in SE,but have not in PE. TUNEL expression are increasing from NE,EH to EAC.Those are:EAC>EH>NE(P<0.05).AH>CH>SH(P<0.01). In the EAC.TUNEL expression are associated with HG and clinical stages: WDEA> MDEA>LDEA, I > II >III,and with the differentiation becoming poor and the clinical stages elevating, TUNEL expression are decreasing(p<0.01). Though [=50]>[<50}; [>l/2]> [=1/2], the differences are not signify cant(p>0.05).9. There are negative correlations between expression of PCNA and TUNEL in AH and EAC(r=-0.943,p<0.01;r=-0.976,p<0.01,respectively). Conclusions:1. ER may have some functions in the NE.ER expression are different in various endometriums:EH>NE>EAC,SH>CH>AH(P<0.05),which suggested ER put important effect in development of EAC.ER expression are not associated with ages.myometrial invasion and clinical stages,but it is correlated with HG. With the differentiation becoming poor, ER expression are decreasing,which provided important evidence for pathological diagnosis.2. PTEN expression are gradually decreased from NE, EH to EAQand the differences are significant,which suggested loss of PTEN expression are involved in the development of EAC.From SH,CH to AH,PTEN expression are also gradually decreased, suggesting loss of PTEN expression put important effect in progression of EH. The differences of PTEN expression are not significant in different ages types,DMI,HG and clinical stages,which means PTEN are not correlated with histopathological characters.PTEN also has no relation with ages.3. No correlation between PTEN and ER expression in the epithelial cells of both AH and EAC.lt is possible that PTEN expression are not affected by estrogen.4. bcl-2 and bax have become increasing from SH.CH to AH(P<0.05), which suggested they participate in the origin of precancerous lesions.5. In EAC,bcl-2 expression have no correlations with ages and myometrial invasion,but it is associated with the HG and clinical stages:WDEA<MDEA<LDEA(P<0.01).III~IV< II < I . bax expression have no significant correlations with ages and clinical stages.With the differentiation becoming poor and myometrial invasion deeping,bax expression are decreasing,and its expression are associated with HG and DMI.So to a certain extent,bcl-2 and bax expression may reflect the differentiation grades and biological behavior. They could be an important parameter for the prognosis of patients.6. There are positive correlations between expression of bcl-2 and bax in EAC,which means bcl-2 and bax jointly put important role in the development of EACHowevert there are no negative correlations between expression of bcl-2 and bax in PE and SE.7. PCNA expression are increasing from NE, EH to EAC,which suggested it involved in carcinogenesis of human EAC. There are some significant differences among PCNA expression of various HG,clinical stages and myometrial invasion/Those are: LDEA> MDEA>WDEA; III> I ,III> II; [>l/2]>[=l/2].With the results,we suspected PCNA put important effect in progression of EAC and could be an important parameter for the clinical diagnosis and prognosis of patients.8. TUNEL expression are increasing from NE, EH to EAC. Those are:EAC>AH>CH>SH>NE.We suspected apoptostic cells are increasing with the hyperplasia of epithelial cells.TUNEL expression are associated with HG and clinical stages,and with the differentiation becoming poor and the clinical更多还原