MMP-9和Ezrin在子宫内膜癌中的表达及与ER、PR的相关性

目的检测MMP-9和Ezrin在不同类型子宫内膜中的表达情况及与雌、孕激素受体的相关性,探讨其在子宫内膜癌发生、发展中的意义。方法采用组织芯片技术及免疫组织化学方法检测和分析MMP-9和Ezrin在子宫内膜癌43例、子宫内膜不典型增生18例、单纯性增生及复杂性增生20例及正常增生期子宫内膜20例中的表达情况及与雌、孕激素受体的相关性。结果 MMP-9和Ezrin在正常增生期子宫内膜,单纯、复杂性增生,不典型增生及子宫内膜癌中的阳性率呈上升趋势,差异有统计学意义(P<0.01)。MMP-9表达强度在子宫内膜癌FIGO分期之间、浅深肌层浸润组间及有无淋巴结转移组间差异有统计学意义。Ezrin表达强度在子宫内膜癌浅深肌层浸润组间和组织类型间差异有统计学意义。MMP-9与Ezrin在子宫内膜癌上表达呈正相关(P<0.05),而Ezrin与ER在子宫内膜癌上表达呈负相关(P<0.05)。结论 MMP-9与Ezrin在子宫内膜癌的发生、浸润转移中起促进作用,Ezrin可能参与了雌激素受体阴性肿瘤的扩散和转移。     

Galectin-1及Galectin-9 在子宫内膜癌组织中的表达

目的:分别检测Galectin-1及Galectin-9在正常子宫内膜组织、子宫内膜不典型增生及子宫内膜腺癌组织中的表达,研究两者与子宫内膜癌发生、发展的关系。方法:收集正常子宫内膜组织30例,子宫内膜不典型增生组织20 例,子宫内膜腺癌组织51例,所有标本均在同一条件下,采用免疫组化法对Galectin-1及Galectin-9表达进行检测。结果:Galectin-1在正常子宫内膜组织、子宫内膜不典型增生及子宫内膜腺癌中的阳性表达率分别为30.0%、70.0%、90.2%;Galectin-9在正常子宫内膜组织、子宫内膜不典型增生及子宫内膜腺癌中的阳性表达率分别为20.0%、75.0%、78.4%。Galectin-1及Galectin-9在子宫内膜腺癌组及子宫内膜不典型增生组中的阳性表达率明显高于正常子宫内膜组,差异有统计学意义（P＜0.05）,但在子宫内膜腺癌组及子宫内膜不典型增生组间差异无统计学意义（P>0.05）。Galectin-1在子宫内膜腺癌不同组织分级、病理分期、肌层浸润程度及是否伴淋巴结转移间表达强度无显著性差异（P>0.05）。Galectin-9 表达强度在子宫内膜腺癌不同组织分级、病理分期、是否伴淋巴结转移与肌层浸润程度间均有统计学差异（P＜0.05）。结论:Galectin-1及Galectin-9均与子宫内膜癌的发生过程相关,相对于Galectin-1,子宫内膜组织中Galectin-9的表达变化与子宫内膜病变的发生更密切,可作为对子宫内膜癌进行早期诊断和治疗效果监测的指标之一,对提高子宫内膜癌的诊治水平具有重要意义。     

MiR-106a 在子宫内膜癌中的表达及意义

目的  检测miR-106a 在子宫内膜癌、不典型增生及正常子宫内膜组织中的表达,探讨它们与子宫内膜癌发生、 发展、侵袭和转移的关系。方法  收集40例子宫内膜癌患者、20例子宫内膜不典型增生患者及30例子宫内膜正常的患者（包 括异常子宫出血及子宫肌瘤患者）的组织标本,应用poly（A）-RT-qPCR 技术,检测miR-106a 在三种不同子宫内膜组织 中的表达,并分别将检测结果和子宫内膜癌患者的临床及病理资料进行统计学分析。结果  miR-106a 在子宫内膜癌、不典 型增生及正常子宫内膜组织中的相对表达量分别为0.667（0.197,1.624）,0.245（0.064,0.759）和 0.104（0.003,1.350）, 表达量逐渐下降,3组间差异有统计学意义（P＜0.01）,子宫内膜癌组织中miR-106a的表达显著高于正常子宫内膜组织（P ＜ 0.01）,同时高于不典型增生组织（P ＜ 0.05）,而不典型增生与正常子宫内膜组织相比较,其差异无统计学意义（P ＞0.05）;miR-106a在Ⅲ+Ⅳ期子宫内膜癌患者中的表达量高于Ⅰ+Ⅱ期;有淋巴结转移的患者中的表达量高于无转移者, 差异均有统计学意义（P ＜ 0.05）;不同年龄、病理类型、病理分级、肌层浸润深度及ER、PR 是否阳性子宫内膜癌患者 中其表达量的差异无统计学意义（P ＞ 0.05）。结论  miR-106a 在子宫内膜癌组织中高表达,可能作为癌基因调控子宫内 膜癌的发生及发展。     

bcl-2、p53和PCNA子宫内膜增生与内膜癌的表达

[目的]探讨bcl-2、p53蛋白和增殖细胞核抗原（PCNA）表达与子宫内膜增生性病变和内膜癌的关系。[方法]应用免疫组织化学ABC法对子宫内膜场50例,不典型子宫内股增生、复杂型子宫内膜增生和单纯型内膜增生各15例,进行bcl－2、p53蛋白和PCNA的检测。[结果]bcl－2、p53在内膜癌、不典型子宫内膜增生、复杂型子宫内膜增生的表达分别为64．0％和52.0％,40．0％和20．0％,13．3％和0,单纯型子宫内膜增生表达均为阴性。内膜癌、内膜不典型增生及复杂型单纯型增生三者之间差异有显著性（P＜0．01）。PCNA在子宫内膜癌、不典型子宫内膜增生表达为100．0%和73.3%,显著高于复杂型及单纯型子宫内膜增生（26．7%和20.0％,P＜0．05）。本实验发现p53和PCNA与内膜癌分化程度,转移扩散有关（P＜0．05）,与临床分期,肌层浸润之间无显著相关性（P＞0．05）。bcol－2与内膜癌分化程度有关,与转移、扩散、分期及肌层浸润之间无显著相关性。[结论]p53和PCNA联合检测可以作为子宫内膜癌预后判断的良好指标。bcl－2与PCNA在不典型内膜增生内有较高表达,是癌变危险因素,联合检测有较高价值。     

结肠癌转移相关基因1与c-met在子宫内膜癌中的表达及其临床价值

目的:探讨MACC1与c-met蛋白在子宫内膜癌中的表达及其临床意义。方法:应用免疫组织化学方法检测45例子宫内膜癌组织、38例增生子宫内膜组织、20例正常子宫内膜组织中MACC1与c-met蛋白的表达情况,分析两者在不同子宫内膜中的表达率及其与子宫内膜癌临床病理参数的关系,并分析两指标在子宫内膜癌组织中表达的相关性。结果:MACC1与c-met在子宫内膜癌组织中的阳性表达率显著高于增生子宫内膜组织、正常子宫内膜组织（P＜0.05）。MACC1与c-met在子宫内膜癌组织中的表达与肌层浸润深度、手术病理分期、组织分化级别显著相关,而与年龄、肿瘤大小等无关。MACC1与c-met蛋白的表达呈正相关（P＜0.05）。结论:MACC1与c-met在子宫内膜癌组织中表达增高,肌层浸润较深、手术病理分期越晚、组织分化程度较低者表达率更高,两者与肿瘤的发生、发展、转移关系密切。     

BRMS1 mRNA和CD44V6 mRNA在子宫内膜癌组织中的表达及意义

目的：探讨乳腺癌转移抑制基因 （breast cancer metastasis suppressor 1,BRMS1） mRNA和CD44V6 mRNA的异常表达与子宫内膜癌侵袭及转移的关系.方法：采用逆转录多聚酶链反应（RT-PCR）法,检测42例子宫内膜癌、12例子宫内膜不典型增生和 15例正常子宫内膜组织中BRMS1 mRNA和CD44V6 mRNA的表达情况,分析其与各种临床参数的关系.结果：1）子宫内膜癌患者的BRMS1基因表达率为37.5%,明显低于不典型增生的75.0%和正常内膜的86.7%;与临床分期（χ^2=4.978）、肌层浸润深度（X^2=5.299）及淋巴结转移（χ^2=4.200）均密切相关,P值均＜0.05; 2）子宫内膜癌患者的CD44V6基因表达率为69.0%,显著高于不典型增生的16.7%和正常内膜的0,P＜0.01; 与临床分期（X^2=5.802）及淋巴结转移（X^2=5.570）均密切相关,P值均＜0.05;3）BRMS1与CD44V6 mRNA的阳性表达率之间无相关关系,肯德尔相关系数为0.069,P＞0.05.结论： BRMS1和CD44V6 mRNA的异常表达是子宫内膜癌发生发展、浸润转移的重要分子学改变,同时检测两者可作为临床预测和评估其侵袭及转移的重要参考指标.     

子宫内膜癌组织中 miR-10a 及 let-7i 的表达及临床意义

目的 探讨 miR-10a 及 let-7i 在子宫内膜癌组织中的表达及意义。方法 选取子宫内膜癌组织40 例、子宫内膜不 典型增生组织20例及正常子宫内膜组织30例,采用多聚腺苷酸加尾实时荧光定量逆转录聚合酶链反应[poly（A）-RT-qPCR] 测定miR-10a 及 let-7i 在三种子宫内膜组织中的表达,并将结果与临床及病理资料进行分析。结果 miR-10a 在子宫内膜癌 组织中高表达（高于正常及不典型增生的子宫内膜组织,P＜0.01）;在病理分级为3级的患者中高表达（高于1+2级者）; 在Ⅲ+Ⅳ期患者中高表达（高于Ⅰ+Ⅱ期者）;在有淋巴结转移的患者中高表达,在深肌层浸润（浸润深度≥1/2）的患者 中高表达;差异显著（P ＜ 0.05）。在不同年龄、雌激素受体（ER）及孕激素受体（PR）是否阳性的子宫内膜癌患者中其 表达量差异无统计学意义（P ＞ 0.05）。let-7i 在子宫内膜癌组织低表达（低于正常和不典型增生的子宫内膜组织,P ＜ 0.01）。结论 在子宫内膜癌组织中miR-10a 表达上调,let-7i 表达下调,miR-10a 可能参与并促进了子宫内膜癌的侵袭 和转移。     

PTEN蛋白在子宫内膜癌组织中的表达及临床意义

目的 探讨抑癌基因PTEN在子宫内膜癌中表达及临床意义.方法 采用免疫组化法检测子宫内膜癌、子宫内膜不典型增生和正常子宫内膜组织中PTEN蛋白的表达,并分析其与临床的相关性.结果 子宫内膜癌组织中PTEN的表达缺失率明显高于子宫内膜不典型增生和正常子宫内膜(P＜0.001),而与增生的严重程度、病理分级有关(P <0.05),但与肌层浸润深度和淋巴结转移无明显相关(P >0.05).结论 PTEN蛋白的表达缺失与子宫内膜癌的发生有关,其在子宫内膜不典型增生发展到子宫内膜癌起到重要作用.     

乙酰肝素酶蛋白与子宫内膜癌临床病理特征的关系研究

目的：研究乙酰肝素酶（heparanase,Hpa）在子宫内膜癌中的表达,并探讨其临床意义.方法：采用免疫组织化学SP法检测48例子宫内膜癌组织中Hpa蛋白的表达情况.结果：Hpa蛋白在子宫内膜癌中阳性率显著高于正常子宫内膜、子宫内膜增生症（P＞0.05）.单因素分析表明浸润不超过内1/2肌层者的Hpa蛋白阳性率显著低于浸润达到外1/2肌层者（P＞0.05）.有淋巴转移组的Hpa蛋白阳性率显著高于无淋巴转移组（P＞0.05）.Ⅰ-Ⅱ期组的Hpa蛋白阳性率显著低于Ⅲ-Ⅳ期组（P＞0.05）.弥漫型内膜癌中Hpa蛋白阳性率高于局限性（P＞0.05）.中、低分化内膜癌中Hpa表达与细胞分化无关（P＞0.05）.多因素Logistic回归分析结果表明Hpa蛋白表达只与淋巴转移、临床分级及肌层浸润显著相关（P＜0.05）.结论：Hpa在子宫内膜癌的阳性率显著高于正常子宫内膜、子宫内膜增生症.Hpa表达与转移、临床分期显著相关.     

子宫内膜癌中的Bmi-1表达及其与hTERT的关系

目的:研究Bmi-1、hTERT在子宫内膜癌、子宫内膜不典型增生、正常子宫内膜组织中的表达。方法:应用免疫组化检测105例子宫内膜癌、40例子宫内膜不典型增生、20例正常子宫内膜组织中Bmi-1、hTERT的表达。结果:在子宫内膜癌、子宫内膜不典型增生和正常子宫内膜组织中Bmi-1、hTERT阳性率分别为86.7%、55%和25%，94.3%、72.5%和5%。Bmi-1在子宫内膜癌和子宫内膜不典型增生中的表达均高于正常子宫内膜组，差异有统计学意义（P<0.05）。子宫内膜癌中，Bmi-1与浸润深度、血管浸润相关，差异有统计学意义（P<0.05），hTERT与组织学分级、组织学类型、浸润深度和血管浸润相关（P<0.05）。Bmi-1和hTERT呈正相关（P<0.01)。结论:Bmi-1和hTERT共同参与子宫内膜病变的恶性转化，联合检测Bmi-1和hTERT对早期判断子宫内膜癌的发生、发展有一定价值。     

Study on the long-term follow-up of endometrial hyperplasia

Background A follow-up study of patients with endometrial hyperplasias was performed in order to clarify whether or not hyperplasias were precursor lesions of endometrial carcinoma in a Japanese population. Methods One hundred and seventy-one patients with various endometrial hyperplasias; 88 with simple, 57 with complex, 12 with simple atypical, and 14 with complex atypical hyperplasias were followed up to evaluate the fate of the lesions as well as their clinical features. The follow-up period ranged from 12 to 195 months (mean, 46). Results The patient ages at the time of the initial diagnosis ranged from 27 to 55 years (mean, 44.5) with simple, 16 to 60 (mean, 43.8) with complex, 33 to 53 (mean, 44.8) with simple atypical, and 29 to 50 (mean, 39.7) with complex atypical hyperplasias. More than 85% of the patients complained of metrorrhagia. Menstrual cycles were irregular in 40% of the cases. Cyclic ovulatory phases measured with basal body temperature were observed in 33.9% of patients with simple, 25.6% with complex, and 22.2% with simple atypical, whereas these were only seen in 8.3% of the cases with complex atyical hyperplasia. Ovulatory disturbances were found in more than 65% of the patients with increasing frequency, depending on the severity of hyperplasia. Only 1 (1.1%) of 88 simple, 1 (3.5%) of 57 complex, and 1 (8.1%) of 12 simple atypical cases progressed to endometrial carcinoma, whereas 3 (21.4%) complex atypical cases progressed to endometrial carcinoma. The incidence of complex atypical is significantly higher than in the former two (P<0.001,P<0.05). The 7 patients who progressed to carcinoma had been followed for 16 to 73 months (mean, 38). Their histological type was either G1, G2 or adenoacanthoma and their FIGO surgical stage was l in all cases. The progression rates of the patients treated with or without cyclic medroxyprogesterone acetate (MPA) were 3.7% and 4.4% respectively, showing no significant differences. The regression rates of each hyperplasia to normal endometrium were 69.4% with simple, 68.4% with complex, 75.0% with simple atypical, and 57.2% with complex atyical hyperplasias. Conclusion Endometrial hyperplasias, especially complex atypical are the precursors to endometrial carcinoma. The strict follow-up of patients with endometrial hyperplasia is mandatory.     

c—myc和p16在子宫内膜癌中的表达及临床意义

目的 研究癌基因c-myc和抑癌基因p16在子宫内膜癌中的表达及临床意义。方法采用免疫组化(S-P)法检测10例增生子宫内膜、22例子宫内膜不典型增生、42例子宫内膜癌中c-myc和p16基因表达,并分析其与子宫内膜癌发生、发展及预后的关系。结果 (1)c-myc在子宫内膜癌中的阳性率为26.19％(11/42),显著高于增生子宫内膜(均显阴性)及子宫内膜不典型增生(4.55％;P<0.05,P<0.05);c-myc在子宫内膜癌中的表达与组织学分级、临床分期显著相关(P<0.01,P<0.05),但与肌层浸润深度及淋巴结转移无关(P>0.05,P>0.05)。(2)p16在子宫内膜癌的阳性率为69.05％(29/42),显著低于增生子宫内膜(100％,10/10)及子宫内膜不典型增生(90.91％,;P<0.05,P<0.05);p16的表达与组织学分级、肌层浸润深度、临床分期及淋巴结转移显著相关(P<0.05,P<0.05,P<0.01,P<0.05)。结论 癌基因c-myc和抑癌基因p16可能在子宫内膜癌的发生、发展及转归中起着重要作用。     

Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium

To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ERalpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.     

子宫内膜癌组织中DcR3的表达及临床意义

目的:检测DcR3在正常增生期子宫内膜、子宫内膜非典型增生和子宫内膜癌组织中的表达,探讨它们在子宫内膜癌发生、发展中的作用.方法:用免疫组织化学法检测DcR3在不同子宫内膜组织中的表达情况.结果:DcR3在子宫内膜癌组织中的表达水平均高于子宫内膜非典型增生和增生期子宫内膜组织(P<0.01).DcR3的表达与子宫内膜癌的临床分期和有无淋巴结转移有关(P<0.05),但与不同病理类型、组织学分级无关(P>0.05).结论:DcR3 在子宫内膜癌的发生、发展过程中可能起着重要的作用.     

PTEN/PI3K信号转导途径与子宫内膜癌生物学行为的相关性

目的 :研究PTEN/PI3K信号转导途径与子宫内膜癌发生发展的关系。方法 :应用免疫组化和免疫印迹方法对 68例子宫内膜癌和癌前病变组织及 11例正常子宫内膜进行PTEN、p PKB及p Bad蛋白检测。结果 :1)PTEN蛋白的阳性表达率在正常增殖期子宫内膜组织中最高 ( 90 9% ) ,非典型增生组织中开始下降 ,在子宫内膜癌组织中明显降低 ( 4 9 1% ) ,三者之间比较 ,差异有统计学意义 ,P <0 0 1;2 )p PKB及p Bad与PTEN的阳性表达呈相反趋势 ,在非典型增生组织及内膜癌组织中p PBK及p Bad表达阳性率明显增加 ,差异均有统计学意义 ,P <0 0 1,P <0 0 5。在子宫内膜癌PTEN表达阴性组织中p PKB、p Bad蛋白染色积分均明显高于PTEN阳性组 ,P <0 0 5 ,P <0 0 1;3 )相关分析显示PTEN与p PKB及p Bad表达均呈负相关 ,r =-0 67,P <0 0 5 ;r =-0 65 ,P <0 0 5 ;4)PTEN、p Bad蛋白的阳性表达率在不同的临床分期、组织学分级及不同肌层浸润程度之间比较 ,差异均无统计学意义 ,P >0 0 5 ,而PTEN、p PKB只在临床分期间差异有统计学意义 ,P <0 0 5。结论 :PTEN/PI3K信号转导途径与子宫内膜癌的发生密切相关。伴随PTEN表达缺失 ,p PKB、p Bad阳性表达更加明显 ,提示PTEN蛋白表达可作为子宫内膜癌早期诊断指标和基因治疗靶点。     

Cyclical change of hMSH2 protein expression in normal endometrium during the menstrual cycle and its overexpression in endometrial hyperplasia and sporadic endometrial carcinoma

BACKGROUND: The role of hMSH2 protein, one of the major DNA repair proteins, until now, had not been elucidated in terms of normal endometrial function during the menstrual cycle. The current study was designed to address this issue and to determine whether the expression of hMSH2 is altered in the course of endometrial carcinogenesis. METHODS: Immunohistochemical reactivity with a monoclonal antibody against the hMSH2 protein was examined in endometrial tissue specimens from 45 patients with normal endometrium, 51 patients with endometrial hyperplasia, and 27 patients with endometrial carcinoma. Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) also was studied in the same samples as a measure of the proliferative activity and was compared with hMSH2 expression in each sample. RESULTS: The functional layer of normal endometrium displayed cyclic changes in hMSH2 protein expression during the menstrual cycle, showing positive expression in the proliferative phase and becoming weak to negative in the secretory phase. This expression pattern was similar to that of PCNA. Sixty-three percent of endometrial carcinomas showed strong positivity for both hMSH2 and PCNA expression, and 7.4% had an intensity of hMSH2 protein expression similar to that found in normal proliferative endometrial glandular cells. There was only 1 sample (3.7%) that was completely negative for hMSH2 expression, and 26% of samples were weakly positive for PCNA and hMSH2 protein. All simple hyperplasias and the majority of complex and atypical hyperplasias showed positive immunoreactivity for hMSH2 and PCNA. CONCLUSIONS: This study demonstrates that hMSH2 protein expression changes during the menstrual cycle in parallel with proliferative activity. In most patients with sporadic endometrial carcinoma, the expression of hMSH2 protein is consistent with PCNA expression. In contrast, loss of hMSH2 expression is observed rarely in patients with sporadic endometrial carcinoma.     

KAI1/CD82和E-cadherin在子宫内膜癌的表达

[目的]研究KAI1/CD82与E-cadherin在子宫内膜癌组织中的表达及其与临床病理参数的关系。[方法]采用免疫组织化学EnVision二步法检测76例子宫内膜癌,15例非典型增生子宫内膜和20例正常增生期子宫内膜组织中KAI1/CD82、E-cadherin的表达。[结果]KAI1/CD82在正常增生期子宫内膜、非典型增生内膜、子宫内膜癌的阳性表达率分别为95%、93.3%和60.5%;E-cadherin在正常增生期子宫内膜、非典型增生内膜、子宫内膜癌的异常表达率分别为0、6.67%和55.26%。KAI1/CD82在子宫内膜癌的表达与组织学分级、肌层浸润程度呈负相关(P=0.000,P=0.01)。E-cadherin在子宫内膜癌的表达与组织学分级及组织学类型有关。KAI1/CD82与E-cadherin在子宫内膜癌中的表达呈显著性相关(P<0.01)。[结论]KAI1/CD82表达下调和E-cadherin异常表达增高与子宫内膜癌的进展有关。