增殖细胞核抗原在子宫内膜病变组织中的表达及临床意义

目的:研究增殖细胞核抗原(PCNA)在子宫内膜病变中的表达规律及其在子宫内膜癌的发生、发展及估计患者预后中的临床价值。方法:用免疫组化SP法检测子宫内膜增殖症30例、非典型增生30例、子宫内膜癌90例,共150例作为实验组,分泌期及增生期内膜各30例作为对照组,观察PCNA在不同内膜病变及正常内膜中的阳性表达率。结果:PCNA在正常子宫内膜、子宫内膜增殖症、非典型增生阳性表达率依次呈升高趋势,子宫内膜增殖症与增生期内膜比较差异无统计学意义,P>0.05。而在非典型增生内膜和内膜癌组织中,PCNA表达明显增高,显著高于子宫内膜增殖症和增生期内膜,差异有统计学意义,P<0.01;且PCNA的阳性率与临床分期、细胞分化程度及淋巴转移有关。结论:PCNA与子宫内膜癌的发生和发展密切相关,PCNA表达对于子宫内膜癌的诊断和判断预后有重要意义。     

子宫内膜癌组织中p-PKB及仅含BH3域蛋白的表达及其相关性

目的：研究子宫内膜癌组织中磷酸化PKB、磷酸化Bad及Bim蛋白及mRNA表达水平，并探讨其与子宫内膜癌发生的关系以及三者问表达的相关性!方法：采用免疫组化方法检测11例正常增殖期子宫内膜、13例非典型增生子宫内膜及55例子宫内膜癌组织中D-PKB、P-Bad及Bim蛋白表达情况，以及采用逆转录聚合酶链反应检测上述子宫内膜组织中PKB、Bad及Bim mRNA表达水平：结果：与正常子宫内膜组织比较，子宫内膜癌及非典型增生组织中P-PKB及D-Bad蛋白表达阳性率明显增加（P=0．001；P〈0．001）；而Bim蛋白的表达则显著减少（P〈0．001），差异有显著性：PKB mRNA及Bad mRNA在正常子宫内膜、非典型增生内膜及子宫内膜癌之间表达的阳性率无明显差异（P〉O．05）．只有Bim mRNA在正常子宫内膜组织中表达的阳性率明显高于非典型增生内膜及子宫内膜癌组织（降0．006）。结论：PKB途径的激活与子宫内膜癌的发生密切相关。其激活后可通过多种机制作用于仅舍BH3域蛋白，抑制其促凋亡活性．导致子宫内膜细胞过度增殖以及子宫内膜癌的发生，     

子宫内膜癌中FasL和Ki67的表达及临床意义

目的:检测子宫内膜癌组织中脂肪酸合成酶配体（fatty acid synthase ligand，FasL）和细胞增殖核抗原（Ki67）的表达情况，探讨二者表达的相关性及临床意义。方法:搜集2012年6月至2015年8月在我院确诊并治疗的82例子宫内膜癌标本作为研究对象，同期选取24例非典型增生子宫内膜标本和30例正常子宫内膜标本作为对照。采用免疫组化法检测不同子宫内膜组织中Ki67、FasL蛋白表达水平，分析Ki67、FasL与子宫内膜癌各项临床病理参数的相关性。采用Spearman对Ki67与FasL的相关性进行分析。结果:Ki67、FasL在正常子宫内膜、非典型增生内膜及子宫内膜癌组织中阳性率均逐渐增加，两两比较差异有统计学意义（P<0.05）。Ki67、FasL表达与子宫内膜癌患者FIGO分期、病理分级、淋巴结转移及肌层浸润密切相关(P<0.05)，与患者年龄、月经状态、脉管瘤栓形成无明显相关性（P>0.05）。经Spearman相关性分析，子宫内膜癌组织中Ki67与FasL表达呈正相关性（r=0.438，P<0.05）。Ki67高表达者2年存活率明显低于低表达者（61.76% vs 92.86%，P<0.05）；FasL高表达者2年存活率明显低于低表达者（57.14% vs 88.46%，P<0.05）。结论:Ki67、FasL在子宫内膜癌组织中显著高表达，有望共同作为诊断子宫内膜癌及判断患者预后的有效生物标志物。     

细胞增殖核抗原Ki-67在子宫内膜腺上皮的表达及其临床意义

目的通过观察增殖细胞核抗原Ki-67在子宫内膜腺上皮的表达，探讨其在子宫内膜生理及病理学变化及意义。方法用免疫组化EnVision二步法对99例子宫内膜诊刮样本组织标记。结果14例呈分泌反应、15例萎缩、24例增生、8例不典型增生、38例子宫内膜原发癌（I型25例，II型13例）腺上皮ki-67表达率分别为0％、33．3％、83．3％，75．0％、57．9％（I型44．0％，II型84．6％）。结论ki-67与子宫内膜增殖有关，分泌反应缺失表达；Ki-67的表达与子宫内膜癌的分类有关。     

Maspin和Ki67在子宫内膜癌中的表达及其相关性分析

目的:探讨在正常子宫内膜、子宫内膜增殖症(非典型)和子宫内膜癌中Maspin和Ki67的表达、相关性及与临床病理特征的关系.方法:采用免疫组织化学方法检测Maspin和Ki67在30例正常增生期子宫内膜、40例子宫内膜增殖症(非典型)和72例子宫内膜癌中的表达.结果:在子宫内膜癌中,Ki67表达分别显著高于正常子宫内膜和子宫内膜增殖症(P =0.043;P =0.020),Maspin表达分别显著高于正常子宫内膜和子宫内膜增殖症(P ＜0.05);Ki67与子宫内膜癌的组织学分级和分期有统计学差异(P＜0.05),Maspin与子宫内膜癌的组织学分级、分期和淋巴结转移有统计学差异(P＜0.05),Maspin和Ki67表达呈正相关(r=0.231,P =0.005).结论:在子宫内膜癌中,Maspin和Ki67的表达提示两者可能成为子宫内膜癌的预后因子.     

PCNA和pRb2/p130在子宫内膜癌中的表达及临床意义

目的：探讨增殖细胞抗原（ PCNA）和pRb2/p130在正常子宫内膜、子宫内膜增殖症、非典型子宫内膜增殖症和子宫内膜癌中的表达、相关性及与临床病理特征之间的关系。方法：免疫组织化学EnVision二步法检测PCNA和pRb2/p130在30例正常增生期子宫内膜、30例子宫内膜增殖症、40例非典型增生子宫内膜增殖症和76例子宫内膜癌中的表达。结果：PCNA在非典型子宫内膜增殖症、子宫内膜癌中的表达分别高于正常子宫内膜和子宫内膜增殖症,差异显著（ P＝0.043;P＝0.020）,pRb2/p130的表达分别低于正常子宫内膜和子宫内膜增殖症,差异显著（ P﹤0.05）;子宫内膜癌中,PCNA与肿瘤大小、分期、淋巴结转移和雌激素差异显著（P﹤0.05）,PCNA在子宫内膜癌中的表达显著高于子宫内膜增殖症（P＝0.045）,pRb2/p130与年龄、组织学分级、浸润深度、淋巴结转移和雌激素有差异（ P﹤0.05）,pRb2/p130和PCNA呈负相关（ r＝-0.331,P＝0.003）。结论：pRb2/p130和PCNA在非典型子宫内膜增殖症和子宫内膜癌中的异常表达,结合在一起可能成为评估识别具有高风险的子宫内膜癌患者的新参数。     

子宫内膜增生与内膜癌增殖细胞核抗原表达及AgNOR计数关联研究

应用抗增殖细胞核抗原（PCNA）的单克隆抗体，以ABC免疫组织化学方法及银染色方法对112例子宫内膜标本进行测定，并与病理学诊断进行对比分析。结果表明：在各种类型的子宫内膜中，PCNA的表达及AgNOR计数依病变的进展明显递增。子宫内膜癌组PCNA表达及AgNOR计数明显高于正常子宫内膜组及子宫内膜增生组（增殖期例外），各组相互比较有显著差异（P＜0．01）。此种方法是测定子宫内膜增生细胞增殖分数的有效手段。对于判断其生物学行为及预后有重要意义，可做为临床判断良恶性子宫内膜增生的指标之一。     

PTEN和CyclinA蛋白在子宫内膜癌组织中的表达及临床意义

目的：探讨PTEN和CyclinA在子宫内膜癌中的表达及其在癌发生发展中的作用。方法：采用免疫组化SP法检测PTEN和CyclinA蛋白在30例正常子宫内膜、30例子宫内膜增生、20例子宫内膜不典型性增生、55例子宫内膜癌组织中的表达。结果：不典型增生组和子宫内膜癌组中PTEN阳性表达率分别为55．00％（11／20）、45．45％（25／55），与全部为阳性表达的正常内膜及阳性表达率为90．00％（27／30）的子宫内膜增生组比较，不典型增生组和癌组中PTEN阳性表达均显著低于正常子宫内膜和子宫内膜增生组（P〈0．05）。CyclinA在不典型增生组和癌组中阳性表达率分别为45．00％（9／20）、67．27％（37／55），显著高于全部阴性表达的正常子宫内膜组和子宫内膜增生组（10．00％，3／30）（P〈0．05）。两者在不典型增生和子宫内膜癌组中的表达均呈显著性负相关（r=-0．5330，r=-0．5556；P〈0．001）。癌组中PTEN阳性表达的缺失与组织学分级有关（P〈0．05），但与肿瘤的浸润转移、临床分期和复发无关（P〉0．05）；CyclinA的阳性表达率与组织学分级、肿瘤的浸润转移和临床分期、复发有关。结论：PTEN表达缺失和CyclinA的过度表达涉及子宫内膜癌的发生、发展过程，二者联合检测可作为子宫内膜癌早期诊断、判断肿瘤生物学行为的免疫学指标。     

Ki—76抗原在原发性胆囊癌中的表达及其意义

目的 探讨Ki－67抗原表达与原发性胆囊癌病理生物学行为的关系。方法 采用免疫组化S－P法，检测胆囊良、恶性病变中Ki－67抗原的表达情况，以其表达阳性率评估胆囊癌组织的增生活性。结果 Ki－67抗原在胆囊癌组织中的表达量显著高于胆囊良性病变（P＜0．01）。但Ki－67抗原的表达强度与胆囊癌组织学类型、Nevin分期及病理分级无明显相关性（P＜0．05），与胆囊癌的突变型p53基因产物表达量明显正相关（P＜0．05）。结论 Ki－67抗原作为1个代表增殖活性的肿瘤标志，其过量表达是胆囊癌高度恶性的生物学行为的客观指标之一，对胆囊恶性肿瘤的病理诊断有较高的实用价值。p53基因可能通过基因突变增强胆囊癌细胞的增殖活性，从而使Ki－67抗原表达量明显增加。     

子宫内膜癌DNA错配修复基因hMSH2表达的研究

目的：探讨DNA错配修复基因hMSH2的表达与子宫内膜癌的关系.方法：选取天津医科大学总医院1981年1月～2001年12月间住院手术子宫内膜癌104例和正常子宫内膜35例（增生期17例，分泌期18例）及8例子宫内膜非典型增生组织标本，采用免疫组化SABC法检测组织中hMSH2基因蛋白表达情况，并对hMSH2蛋白表达与子宫内膜癌临床病理特征的关系进行分析.结果：子宫内膜癌、子宫内膜非典型增生、正常子宫内膜增生期和分泌期hMSH2表达缺失率分别为68.3%、4/8（50.0%）、5.9%和5.6%，子宫内膜非典型增生和子宫内膜癌组织hMSH2表达缺失率无明显差异（P=0.294），但明显高于正常增生期及分泌期子宫内膜 子宫内膜样腺癌、腺鳞伴鳞状上皮分化、透明细胞癌和浆液性癌hMSH2表达缺失率分别为73.3%、2/8、2/4和1/2，子宫内膜样腺癌中hMSH2基因表达缺失率明显高于其它组织学类型（P=0.035）.hMSH2表达阴性和阳性者5年生存率分别为80.0%、52.0%，10年生存率分别为78.0%、32.0%，hMSH2基因表达阴性者生存率明显高于阳性表达者.结论：子宫内膜癌和子宫内膜非典型增生中hMSH2基因表达缺失率相似，hMSH2表达缺失可能与子宫内膜癌发生早期有关.hMSH2基因表达缺失与子宫内膜癌组织学类型中的子宫内膜样腺癌有关，hMSH2基因表达缺失者预后较好.     

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.     

Significantly decreased P27 expression in endometrial carcinoma compared to complex hyperplasia with atypia (correlation with p53 expression)

P27 expression was examined on paraffin-embedded specimens in proliferative, secretory, hyperplastic and neoplastic human endometrium by immunohistochemistry. The results of p27 immunoreactivity in endometrial carcinomas were compared with clinicopathological indicators as well as with p53 expression. Thirty-eight cases of endometrial carcinoma, 30 normal functional (15 proliferative, 15 secretory), 24 hyperplastic endometrium (12 without atypia, 12 with atypia) specimens were studied by using monoclonal p27 and p53 antibodies. The streptavidin-biotin-peroxidase detection system was used and the intensity and the distribution of immunoreactivity was evaluated semiquantitatively. p27 expression was present both in the proliferative and secretory phases; the expression being stronger in the secretory period. In complex hyperplasia with atypia, p27 expression was even higher and it was significantly reduced in the endometrial carcinoma group (p<0.05). No significant correlation was found between p27 expression and any of the clinicopathologic prognostic parameters (p>0.05). Nuclear p53 expression was detected in 13 (34.2%) patients with endometrial carcinoma and was higher in non-endometrioid carcinomas and in tumors with increasing FIGO grade (p<0.05). High expression of p53 was not found to be a significant prognostic indicator of survival (p> 0.05). No p53 expression was detected in the endometria with proliferation, secretion or hyperplasia either simple without atypia or complex with atypia. Surprisingly, tumors with absent/low p27 expression showed absent/low p53 expression. Our data suggest that p27 is necessary to control the proliferation of endometrium and its loss of expression seems to play a role in some aspects of endometrial carcinogenesis.     

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.     

Importin 13在子宫内膜异位症和子宫内膜癌中的表达及意义

背景与目的:正常情况下的子宫内膜干/祖细胞有助于子宫内膜的生理性修复,而子宫内膜干/祖细胞的异常增殖和异常分化则会导致子宫内膜疾病(如子宫内膜异位症和子宫内膜癌)。Importin 13(IPO13)是importinβ家族新成员的一个核质双向的转运受体蛋白,是角膜上皮干细胞的一个标记,在维持干细胞的性状、高增殖潜力、低分化状态,调节细胞分化以及小鼠生殖细胞减数分裂上具有重要的作用。本文探讨成体干细胞标记IPO13在子宫内膜异位症和子宫内膜癌中的表达及意义。方法:手术取正常子宫内膜组织40例(对照组),其中增生期和分泌期各20例,异位子宫内膜组织20例(异位症组)和子宫内膜癌病灶组织20例(内膜癌组)。采用免疫组化SP法检测IPO13蛋白在细胞内的定位;采用实时荧光定量PCR技术(real-time quantitativepolymerase chain reaction,RT-PCR)检测IPO13 mRNA的表达;Western blot检测IPO13蛋白的表达。结果:IPO13蛋白在内膜癌、异位症及正常对照组中腺上皮细胞和间质细胞的细胞质和细胞核中均有表达。IPO13蛋白在对照组增生期表达量(0.52±0.30)明显高于分泌期(0.25±0.04,P<0.05);IPO13蛋白在异位症组表达量(0.81±0.12)明显高于对照组增生期及分泌期(P<0.05);IPO13蛋白在内膜癌组表达量(1.21±0.11)明显高于异位症组(P<0.05)。IPO13 mRNA在对照组增生期表达量是分泌期的3倍(P<0.05);IPO13 mRNA在异位症组中表达量是对照组分泌期的6倍(P<0.05),增生期的2.5倍(P<0.05);IPO13 mRNA在内膜癌组表达量是异位症组的2倍(P<0.05)。结论:IPO13在子宫内膜癌中及异位症组中表达明显高于对照组,推测其高表达与子宫内膜癌及子宫内膜异位症发病密切相关。