子宫内膜样腺癌组织中p27、MCM7蛋白的表达及意义

目的 探讨p27、MCM7蛋白在子宫内膜样腺癌及其癌前病变组织中的表达及意义。方法 采用免疫组织化学SP法检测30例正常子宫内膜、30例内膜增生、30例非典型增生和50例子宫内膜样腺癌组织中p27和MCM7蛋白的表达情况。结果 27蛋白的阳性表达水平在正常子宫内膜、内膜增生、非典型性增生到子宫内膜样腺癌组织中呈逐渐下降趋势,组间两两比较差异均有统计学意义（P<0.05）;而MCM7阳性表达水平呈逐渐上升趋势,子宫内膜样腺癌组和非典型增生组均显著高于正常组和内膜增生组（P<0.05）,子宫内膜样腺癌组中p27与MCM7的表达呈负相关（r=-0.3306,P<0.02）,p27蛋白低表达与组织学分级及手术病理分期有关（P<0.05）,MCM7蛋白的高表达与组织学分级、肌层浸润、淋巴结转移和手术病理分期有关(P<0.05);p27低表达和MCM7的高表达与肿瘤的复发有关（P<0.05）。结论 p27蛋白的表达缺失和MCM7的高表达可能涉及了子宫内膜样腺癌的发生、发展过程,两者的联合检测可望作为临床早期诊断、评价预后的生物学指标。     

子宫内膜中PTEN、p16蛋白的表达及临床意义

目的：研究子宫内膜组织中PTEN、p16蛋白的异常表达,探讨其与子宫内膜癌变的关系和早期诊断及评判预后的可能性。方法：应用免疫组化S—P法对20例正常子宫内膜组织、40例子宫内膜增生症组织、30例内膜腺癌组织中PTEN、p16蛋白的表达进行研究。结果：在正常增生期子宫内膜、子宫内膜增生症（单纯型增生、复杂型增生、不典型增生）、子宫内膜腺癌组织中PTENp16蛋白的阳性表达率呈递减趋势,子宫内膜腺癌与除不典型增生外的子宫内膜增生症组织及正常子宫内膜组织的glEN蛋白表达差异有显著性（P〈0．05）,正常子宫内膜、单纯型增生与不典型增生组织的PTEN蛋白表达差异有显著性（P〈0．05）,子宫内膜腺癌与正常子宫内膜及单纯型增生子宫内膜p16蛋白表达差异有显著性（P〈0．05）,正常子宫内膜与增生症子宫内膜差异无显著性（P〉0．05）增生症子宫内膜各组间p16蛋白表达无显著性差异（P〉0．05）,PTENP16蛋白的表达与子宫内膜癌的手术分期、组织学分级,肌层浸润有关（P〈0．05）。PTEN、p16蛋白表达存在正相关性（r=0．978,P〈0．05）。结论：PTEN、p16蛋白的异常表达与子宫内膜的癌变过程相关。     

PTEN、p21ras在人子宫内膜腺癌组织中的表达及其意义

目的探讨PTEN基因、Ki-ras基因在子宫内膜腺癌中的表达及意义。方法采用免疫组织化学S-P法测定20例正常增生期子宫内膜、20例不典型增生子宫内膜及45例子宫内膜腺癌组织中的PTEN、p21ras蛋白表达。结果PTEN在正常子宫内膜、不典型增生和内膜腺癌中的阳性表达率逐渐降低,分别为95.0%、40.0%、31.1%。正常子宫内膜组织中的PTEN阳性表达率显著高于不典型增生和内膜腺癌(P<0.01)。p21ras蛋白在正常子宫内膜、不典型增生和子宫内膜腺癌中的阳性表达率分别为0、50.0%、64.4%,子宫内膜不典型增生和子宫内膜腺癌组均显著高于正常子宫内膜组(P<0.01)。PTEN与p21ras蛋白表达呈负相关(r=-0.303,P<0.05),且均与细胞分化程度显著相关(P<0.05)。结论1)PTEN、ki-ras基因在子宫内膜腺癌发生发展中起重要作用,PTEN是其发生的早期分子事件;2)PTEN、p21ras的蛋白表达与病理分级有关;3)在子宫内膜腺癌中PTEN与p21ras可能参与同一蛋白通路发挥生理作用。     

子宫内膜癌变hMSH6与p53表达的意义

目的 子宫内膜癌因其逐年上升的发病率和年轻化趋势而备受关注,深入研究其癌变机制,对于子宫内膜癌的防治具有重要意义.本研究分析子宫内膜样腺癌、子宫内膜不典型增生和子宫内膜增生不伴非典型性内膜中hMSH6和p56的表达,探讨hMSH6和p53在子宫内膜癌变过程中的表达相关性及临床意义.方法 用免疫组化法检测滨州医学院附属医院病理科2010-08-01-2013-03-01刮宫及手术切除的65例子宫内膜癌,15例子宫内膜不典型增生及20例子宫内膜增生不伴非典型性组织中p53和hMSH6的表达情况,统计学分析其表达水平与临床病理因素之间的相关性.结果 子宫内膜样腺癌组织hMSH6蛋白表达率为27.6％ (18/65),明显低于子宫内膜不典型增生组织75.0％(15/20),及子宫内膜增生不伴非典型性组织73.3％(11/15).子宫内膜样腺癌组织p53蛋白表达率55.3％(36/65),明显高于子宫内膜不典型增生组织13.3％(2/15),及子宫内膜增生不伴非典型性5.0％(1/20),其中子宫内膜样腺癌组hMSH6及p53的表达与子宫内膜不典型增生组及子宫内膜增生不伴非典型性组织相比差异有统计学意义(x2=10.99,P=0.002;x2=10.99,P=0.004),而子宫内膜增生不伴非典型性组织与子宫内膜不典型增生组相比差异无统计学意义,P＞0.05;hMSH6及p53蛋白的表达均与手术病理分期和组织学分级有关,均P＜0.001.结论 hMSH6基因表达缺失及p53蛋白的表达与子宫内膜癌的发生有关,通过检测两者的表达水平可对子宫内膜癌的早期预防,早期诊断提供重要依据.     

子宫内膜样腺癌组织中Maspin蛋白表达及其临床意义

目的探讨Maspin蛋白在子宫内膜样腺癌中的表达及其临床意义。方法采用免疫组化Envision TM二步法,检测67例子宫内膜样腺癌、30例子宫内膜不典型增生、18例正常子宫内膜组织中Maspin蛋白的表达情况。结果Maspin蛋白在正常子宫内膜组织、子宫内膜不典型增生、子宫内膜样腺癌中的阳性表达率分别为16.67%（3/18）、40.00%（12/30）、68.66%（46/67）,3组比较,有显著性差异（χ^2=18.17,P〈0.05）,Maspin蛋白表达与子宫内膜样腺癌的分期、脉管浸润和淋巴结转移相关,与患者年龄、组织学分级和肌层浸润深度无关。结论Maspin蛋白在子宫内膜样腺癌中呈高表达,但随着肿瘤的发展其表达水平下调,其在子宫内膜癌的发生、发展和转移过程中起着一定调控作用。     

子宫内膜中PTEN、p16蛋白的表达及临床意义

目的:研究子宫内膜组织中PTEN、p16蛋白的异常表达,探讨其与子宫内膜癌变的关系和早期诊断及评判预后的可能性.方法:应用免疫组化S-P法对20例正常子宫内膜组织、40例子宫内膜增生症组织、30例内膜腺癌组织中PTEN、p16蛋白的表达进行研究.结果:在正常增生期子宫内膜、子宫内膜增生症(单纯型增生、复杂型增生、不典型增生)、子宫内膜腺癌组织中PTEN p16蛋白的阳性表达率呈递减趋势,子宫内膜腺癌与除不典型增生外的子宫内膜增生症组织及正常子宫内膜组织的PTEN蛋白表达差异有显著性(P＜0.05),正常子宫内膜、单纯型增生与不典型增生组织的PTEN蛋白表达差异有显著性(P＜0.05),子宫内膜腺癌与正常子宫内膜及单纯型增生子宫内膜p16 蛋白表达差异有显著性(P＜0.05),正常子宫内膜与增生症子宫内膜差异无显著性(P＞0.05) 增生症子宫内膜各组间p16蛋白表达无显著性差异(P＞0.05),PTEN P16蛋白的表达与子宫内膜癌的手术分期、组织学分级,肌层浸润有关(P＜0.05).PTEN、p16蛋白表达存在正相关性(r=0.978,P＜0.05).结论:PTEN、p16蛋白的异常表达与子宫内膜的癌变过程相关.     

子宫内膜增生及癌变组织中增殖细胞核抗原与p16和p53基因表达的相关性研究

目的探讨增殖细胞核抗原（PCNA）及基因p16、p53在单纯性子宫内膜增生（ESH）、子宫内膜不典型增生（EAH）和子宫内膜癌（EC）组织中表达情况。方法应用免疫组化法分别对26例EC、28例EAH、24例ESH组织进行PCNA和p16、p53基因蛋白定位及表达程度检测,并对比其差异,分析它们之间的关系。结果PCNA在ESH、EAH和EC3组病例中强阳性表达分别为16．7％、82．1％和96．2％,ESH与EAH、EC比较差异有统计学意义（P〈0．01）,而EAH与EC比较差异无统计学意义（P〉0．05）。p16在ESH、EAH和EC3组病例中阳性表达分别为95．8％、46．4％和50．0％,ESH与EAH、Ec组比较差异有统计学意义（P〈0．05）;EAH与EC组比较差异无统计学意义（P〉0．05）。p53在ESH组无阳性表达病例,EAH组阳性率25％,EC组阳性率65．4％,3组病例之间比较差异均有统计学意义（P〈0．01）。结论PCNA、p53表达在子宫内膜增殖性病变、细胞恶性转化的进程中呈递增趋势,而p16趋于递减,提示细胞的过度增殖和增殖-凋亡相关基因的表达失衡在子宫内膜恶性转化过程中起重要作用。PCNA、p16和p53的异常表达可作为子宫内膜增生性疾病不同发展阶段的诊断及预测其生物学行为的参考指标。     

Glut-1、COX-2在子宫内膜腺癌及其癌前病变中的表达

目的研究Glut-1、COX-2在子宫内膜腺癌及其癌前病变中的表达特点及其诊断价值。方法应用免疫组织化学SP法检测了20例正常增生期子宫内膜、23例单纯性子宫内膜增生、21例复杂性子宫内膜增生、43例非典型性子宫内膜增生、25例子宫内膜腺癌中Glut-1、COX-2的表达。结果Glut-1和COX-2在各实验组中的阳性表达率增生期子宫内膜组为0和10.0%,单纯性增生组为0和9.1%,复杂性增生组为4.8%和14.3%,低级别非典型增生组为20.0%和25.0%,高级别非典型增生组为52.2%和52.4%,腺癌组为88.0%和91.7%;Glut-1、COX-2在各实验组间差异均有统计学意义(P均=0.000),在高级别非典型增生组与子宫内膜腺癌组间差异均有统计学意义(P<0.01)。COX-2与Glut-1在各组的表达呈显著正相关关系(P<0.01)。结论Glut-1、COX-2可能在子宫内膜癌的发生发展中共同发挥重要作用,两者联合检测对子宫内膜腺癌及癌前病变的鉴别诊断有较高的诊断价值。     

p73、PTEN和Ki-67在子宫内膜样腺癌组织中的表达及意义

目的探讨p73、PTEN和Ki-67蛋白在子宫内膜癌前病变及内膜样腺癌中的表达及意义。方法用免疫组化SP法,在13例子宫内膜正常增生期、20例简单型增生过长、22例复杂型增生过长(包括11例不典型增生)及38例内膜样腺癌组织中检测p73、PTEN和Ki-67蛋白的表达情况。结果随着子宫内膜病变的恶性进展,p73和Ki-67蛋白的阳性表达率上调而PTEN下调,且p73和Ki-67表达上调呈显著正相关(P<0.01),Pearson列联系数为0.5144。p73和Ki-67蛋白表达与子宫内膜样腺癌组织分化程度有关(P<0.01),Ki-67和PTEN蛋白表达与子宫内膜样腺癌的临床分期和肌层浸润有关(P<0.05)。结论p73和Ki-67协同调控子宫内膜腺上皮细胞的生长、增殖,并促进癌变;PTEN表达下调是子宫内膜样腺癌的早发事件。联合检测p73、Ki-67和PTEN蛋白的表达可作为在子宫内膜癌早期诊断的参考指标并指导临床早期治疗。     

子宫内膜样腺癌组织中NF-kB p65的表达

目的探讨子宫内膜样腺癌组织中Nf-κB p65的表达及其在子宫内膜样腺癌发生、发展中的机制.方法采用免疫组织化学技术检测38例子宫内膜样腺癌、30例子宫内膜增生过长及10例正常增生期子宫内膜组织石蜡标本中NF-κB p65蛋白的表达,并以CD34为标记志测定子宫内膜样腺癌组织的微血管密度.结果NF-κB p65蛋白在子宫内膜样腺癌、子宫内膜增生过长及正常增生期子宫内膜组织中的表达率分别为65.8%(25/38)、36.7%(11/30)和0,在不典型子宫内膜增生过长中为46.7%(7/15).子宫内膜样腺癌中NF-κB p65蛋白的表达率显著高于子宫内膜增生过长,χ2=5.707,P=0.015 7;与正常增生期子宫内膜相比较差异有统计学意义,P=0.000 2;与不典型子宫内膜增生过长相比较差异无统计学意义,χ2=0.710,P=0.168 8.NF-κB p65蛋白的表达与子宫内膜样腺癌组织分化(χ2=5.788,P=0.017 6)、手术病理分期(χ2=4.677,P=0.033 0)及子宫肌层浸润深度有关(χ2=4.799,P=0.030 2).NF-κB p65蛋白表达阳性患者MVD值为53.6±19.3,阴性表达患者为41.2±16.2,差异有统计学意义,t=1.879,P=0.027 8.结论NF-κB p65是与子宫内膜样腺癌相关的癌蛋白,可能在子宫内膜样腺癌的发生、发展中发挥重要作用.     

Immunohistochemical staining of GLUT1 in benign, hyperplastic, and malignant endometrial epithelia

BACKGROUND: Aberrant expression of the facilitative glucose transporter, GLUT1, is found in a wide spectrum of epithelial malignancies. The current study describes an immunohistochemical study of GLUT1 expression in benign, hyperplastic, and malignant endometrial epithelia. METHODS: One hundred sixteen formalin fixed, paraffin embedded sections of benign, hyperplastic, and malignant endometrial epithelium were immunostained with rabbit anti-GLUT1 antibody using the streptavidin-biotin method. RESULTS: Proliferative, secretory, and atrophic endometrium were not stained with GLUT1 antiserum. Rare, minute foci of tubal metaplasia stained positively. Simple and complex endometrial hyperplasias were consistently GLUT1 negative. All specimens of atypical hyperplasia had foci that were positive for GLUT1. All endometrial adenocarcinomas were GLUT1 positive. CONCLUSIONS: The results of the current study appear to indicate that 1) aberrant overexpression of GLUT1 is a consistent feature of endometrioid adenocarcinoma; 2) GLUT1 immunostaining may be useful in distinguishing benign hyperplasias from hyperplasias that are associated strongly with malignancy; and 3) some or all cases of atypical hyperplasia may be neoplastic rather than hyperplastic, given the existence of a molecular defect common to this hyperplastic subtype and endometrioid adenocarcinoma.     

Defining the extent of cables loss in endometrial cancer subtypes and its effectiveness as an inhibitor of cell proliferation in malignant endometrial cells in vitro and in vivo

Loss of Cables expression is associated with a high incidence of endometrial hyperplasia and endometrial adenocarcinoma in humans. The Cables mutant mouse develops endometrial hyperplasia and following exposure to chronic estrogen develops early endometrial adenocarcinoma. The objectives of the current study were to determine if: (1) loss of Cables expression occurred in high grade endometrioid adenocarcinoma, uterine serous and clear cell carcinoma as observed in endometrial hyperplasia and low grade endometrial adenocarcinoma; (2) overexpression of Cables inhibited cell proliferation in endometrial cancer (EC) cells in vitro and in vivo; and (3) progesterone could regulate the expression of Cables mRNA. Hyperplastic endometrium and low and high grade endometrioid adenocarcinoma showed loss of Cables expression when compared to benign control secretory endometrium. Loss of Cables expression in serous and clear cell tumors was similar to that observed in endometrioid adenocarcinomas with greater than 80% showing loss of protein expression. Treatment of EC lines with progesterone increased cables expression in low-grade EC whereas it had no effect on cables expression in cells derived from high-grade EC. The progesterone-induced increase in cables was abrogated in the presence of a progesterone receptor (PR) antagonist, suggesting the PR mediates the increase. Cables overexpression inhibited cell proliferation of well differentiated EC cells and had no effect on the poorly differentiated EC cells. The capacity to form tumors was dramatically reduced in the Cables overexpressing cell lines compared to those cells containing the control vector. Collectively these results suggest that Cables is an important regulator of cell proliferation and loss of Cables expression contributes to the development of all types of EC.     

Endometrial Intraepithelial Neoplasia (EIN) in Endometrial Biopsy Specimens Categorized by the 1994 World Health Organization Classification for Endometrial Hyperplasia

Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsyspecimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia.Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined andcategorized by the WHO 1994 criteria and for the presence of EIN as defined by the International EndometrialCollaborative Group. β-catenin expression was examined by immunohistochemistry. A total of 474 cases of HEstained endometrial biopsy tissues were reviewed. There were 379 cases of simple endometrial hyperplasia, 16with simple atypical endometrial hyperplasia, 48 with complex endometrial hyperplasia, and 31 with complexatypical endometrial hyperplasia. Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) thatwere classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple endometrial hyperplasia, 1 (6.3%)as simple atypical endometrial hyperplasia, 6 (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) ascomplex atypical endometrial hyperplasia. EIN was associated with a higher rate of β-catenin positivity thanendometrium classified as benign hyperplasia (72% vs. 22.5%, respectively, P < 0.001), but a lower rate thanendometrial adenocarcinoma (72% vs. 96.2%, respectively, P < 0.001). In benign endometrial hyperplasia, highβ-catenin expression was noted in the cell membranes, whereas in EIN and endometrial adenocarcinoma highexpression was noted in the cytoplasm. In conclusion, EIN is more accurate than the WHO classification for thediagnosis of precancerous lesions of the endometrium.     

Role of Morphometry and Matrix Metalloproteinase-9 Expression in Differentiating between Atypical Endometrial Hyperplasia and Low Grade Endometrial Adenocarcinoma

Background: Endometrial carcinomas are common gynecologic malignancies worldwide. In Egypt they represent2.6 %. We evaluated the role of morphometry and MMP-9 immunohistochemical expression to differentiate atypicalendometrial hyperplasia from low grade endometrial adenocarcinoma. Methods: 60 cases of endometrial lesions thatincluded 25 cases of complex endometrial hyperplasia with atypia, 25 cases of low grade endometrioid adenocarcinoma,in addition to 10 cases of proliferative endometrium as a control group. Morphometric measurements and D-scorewere evaluated. MMP9 was performed using streptavidin –biotin immunoperoxidase system. Results: D score wasmore than 1 in 100% of cases of proliferative endometrium. In atypical hyperplasia 28 % of cases had a D-score morethan 1, 44% less than 0 and 28% of cases had a D score between 0 and 1 with uncertain prognosis. All carcinomacases had D-score less than 0. MMP9 was positive in all cases of the study but differ in its degree of expression;proliferative endometrium with low expression. Atypical hyperplasia divided as 52% low expression and 48% highexpression. Most of the Endometrial adenocarcinoma cases (92%) showed high expression. There was significantdifference in expression of MMP9 in atypical endometrial hyperplasia and endometrial adenocarcinoma (p> 0.001).Conclusion: The relation between MMP9 expression and D-score value in cases of atypical endometrial hyperplasiawas highly significant P>0.001Thus, incorporating both MMP9 immunoexpression and D-score value would increasethe accuracy of diagnosis of atypical endometrial hyperplasia and low grade endometrial adenocarcinoma.     

Bcl-2和Bax蛋白在正常、增生和恶性子宫内膜中的表达

Objective To investigate the expression of Bcl-2 and Bax proteins in normal, hyperplastic, and malignant endometrium. Methods Endometrial tissues were obtained from 14 proliferative endometrial samples; simple (n=30) and complex hyperplasia without atypia (n=13); complex hyperplasia with atypia (n=20) and endometrial adenocarcinoma (n=17). The expression of Bcl-2 and Bax proteins was detected by using immunohistochemical staining with appropriate antibodies. Results The intensity of Bcl-2 staining was gradually increased from proliferative to simple and complex hyperplasia, but it was gradually decreased from atypia hyperplasia to endometrial adenocarcinoma (P<0.05). The intensity of Bax staining was gradually increased from proliferative endometrium to simple and complex hyperplasia, but in atypia hyperplasia it was obviously lower than simple hyperplasia, the ratio of Bcl-2: Bax staining intensity was changed with the endometrium from proliferative, hyperplastic endometrium to endometrial adenocarcinoma. The ratio of Bcl-2: Bax staining intensity was obviously decreased in atypia hyperplasia and endometrial adenocarcinoma. Conclusion The survival time of the cells in hyperplasia expressing Bcl-2 might be prolonged. Neoplastic cells in atypia hyperplasia and adenocarcinoma might show a decreased expression of Bcl-2 and Bax, suggesting that Bcl-2 and Bax might be important indexes and prognosis factors and the expression of Bcl-2 and Bax might be correlated with carcinogenesis in the uterine endometrium of humans.     

子宫内膜癌中MUC1和E-cad的表达及其相关性

目的：探讨MUC1和E-cad在子宫内膜样腺癌组织中的表达及其相关性。方法：采用免疫组化En-Vision法检测30例增生期子宫内膜组织、36例单纯性增生内膜、50例不典型增生内膜及55例子宫内膜样腺癌组织中MUC1和E-cad蛋白表达。结果：从增生期子宫内膜→宫内膜单纯性增生→宫内膜不典型增生→子宫内膜样腺癌,MUC1和E-cad的正常表达率逐渐降低,异质表达率逐渐升高（P=0.000）。MUC1和E-cad蛋白表达在子宫内膜样腺癌组织中呈正相关关系（r=0.290,P=0.032）。结论：MUC1和E-cad蛋白异质表达可能与子宫内膜样腺癌的发生有关。MUC1和E-cad在子宫内膜样腺癌的形成过程中可能具有协同作用。