子宫内膜组织ER、PR及PCNA表达与子宫内膜增生过长的关系

目的：探讨子宫内膜增生过长的发病机理，为临床内分泌治疗提供理论基础。方法：应用免疫组织化学Ｓ－Ｐ法，对手术切除和诊刮的６７例不同时期子宫内膜和不同类型增生过长子宫内膜标本进行ＥＲ、ＰＲ和ＰＣＮＡ含量检测分析。结果：ＥＲ、ＰＲ在正常增生期子宫内膜中的含量显著高于分泌期（Ｐ＜０．０１），在单纯性增生过长和复杂性增生过长子宫内膜中ＥＲ、ＰＲ的含量也有显著差异（Ｐ＜０．０１）。各组增生过长子宫内膜中ＥＲ的含量高于ＰＲ（Ｐ＜０．０１）。ＰＣＮＡ在内膜分泌期和伴有非典型增生的子宫内膜中含量高（Ｐ＜０．０１）。结论：ＥＲ主要与子宫内膜增生过长有关，ＰＣＮＡ在非典型增生子宫内膜中过表达可能与宫内膜异常生长有关。     

子宫内膜组织ER,PR及PCNA表达与子宫内膜增生 …

探讨子宫内膜增生过长的发病机理。为临床内分泌治疗提供理论基础，方法：应用免疫组织化学Ｓ－Ｐ法，对手术切除和诊刮的６７例不同时期子宫内膜和不同类型增生过长子宫内膜标本进行ＥＲ，ＰＲ和ＰＣＮＡ含量分析。结果：ＥＲ，ＰＲ在正常增生期子宫人膜中的含量显著高于分泌期，在单纯性增生工和复杂性增生过长宫内膜中ＥＲ，ＰＲ的含量也有显著差异。     

子宫内膜样腺癌中mTOR和eIF4E蛋白表达及临床意义

目的 探讨mTOR和eIF4E蛋白在子宫内膜样腺癌发生中的作用和临床意义.方法 采用免疫组化EliVision方法分别检测17例增殖期宫内膜、64例子宫内膜增生性病变和44例子宫内膜样腺癌中mTOR和eIF4E蛋白的表达情况.结果 mTOR在增殖期子宫内膜和单纯性增生宫内膜中均无强阳性表达,复杂性增生宫内膜和子宫内膜样腺癌中mTOR强阳性表达率分别为23.40%和52.27% ,明显高于增殖期子宫内膜和单纯性增生宫内膜(P<0.05).子宫内膜样腺癌中mTOR的强阳性表达率明显高于复杂性增生宫内膜和复杂性非典型增生中的宫内膜(P<0.05).子宫内膜样腺癌中mTOR强阳性表达与肿瘤分化程度密切相关,Ⅱ、Ⅲ级子宫内膜样腺癌的强阳性表达率明显高于Ⅰ级(72.41% vs 13.33%,P<0.05).而与TNM分期和淋巴结转移均无相关性(P>0.05).eIF4E蛋白在增殖期宫内膜,单纯性增生宫内膜,复杂性增生宫内膜,子宫内膜样腺癌中的阳性表达率分别为52.94%,73.68%,85.11%和90.91%.复杂性增生宫内膜和子宫内膜样腺癌中eIF4E蛋白的阳性表达均明显高于其它各组(P<0.05),但两者差异无显著性(P>0.05).eIF4E与子宫内膜样腺癌分化程度、TNM分期和有无淋巴结转移均无相关性(P>0.05).结论 mTOR、eIF4E蛋白在复杂性增生宫内膜和子宫内膜样腺癌中表达明显增强,提示两者可能在子宫内膜样腺癌发生中发挥一定作用.     

孕激素治疗增生子宫内膜和高分化子宫内膜样癌后的临床病理形态观察

目的：显微镜下观察孕激素治疗对不同增生子宫内膜和高分化子宫内膜样腺癌的组织病理学影响,为临床更好地管理孕激素治疗提供依据。方法：收集2010年至2014年86例增生不伴有非典型增生(包括简单型增生、复杂型增生)和非典型增生及高分化子宫内膜样癌患者在我院经孕激素正规治疗刮宫至少两次以上病例,其中刮宫次数最多者达11次,时间2个月到5年。两个高年资病理医师双盲法显微镜下观察激素治疗前后病理改变。结果：简单型增生50名,基本转归为正常子宫内膜;复杂型增生18名,治疗约半年后转为正常子宫内膜;但其中2例有复发或恶化。非典型增生不伴/伴癌变18例,孕激素治疗后刮宫,10例镜下显示好转或完全缓解。好转病例显示组织结构依然复杂,但腺体间质比例降低,间质蜕膜样变或者玻璃样变;高倍镜下腺上皮细胞核变温和,核膜光滑,核仁不明显,核浆比例降低,胞浆丰富,伴嗜酸性变、鳞状细胞化生或粘液化生。该类病例继续治疗后,转化为正常周期宫内膜。但有4例(22.2%)在1~2年后复查,又出现非典型增生,甚至癌变。另有2个病例,治疗3个月后刮宫,镜下依然为非典型增生改变,证明孕激素治疗无效。结论：1)简单型增生过孕激素治疗效果好,3~6个月后刮宫,基本恢复正常周期。2)对非典型增生及癌变患者,因容易复发和恶化,按2014NCCN诊疗规范治疗坚持用药并定期复查非常有必要。3)非典型增生伴/不伴癌变病例,细胞学好转先于组织学。4)对治疗无效者,需要根据患者生育要求及时手术治疗。5)根据孕激素治疗效果评价,增生不伴非典型增生患者,区分简单型和复杂型增生依然有必要性。     

子宫肌瘤患者的子宫内膜病理特征分析

目的探讨子宫肌瘤患者的子宫内膜病理特征及相关因素。方法选取2007～2008年186例子宫肌瘤患者,分析其子宫内膜病理特征。结果 186例患者中有38例表现阴道不规则流血,单发肌瘤85例,多发肌瘤101例,子宫肌瘤变性27例,43例患者发生子宫内膜病变,包括子宫内膜息肉14例（7.53%）、子宫内膜单纯增生16例（8.61%）、复杂增生5例（2.69%）、非典型增生2例（1.08%）、子宫内膜癌6例（3.23%）。结论子宫肌瘤可同时合并子宫内膜病变及子宫内膜癌,子宫肌瘤单发或多发、子宫肌瘤变性等情况与子宫内膜病变无关。不规则阴道流血、绝经与子宫内膜病变及子宫内膜癌的发生有关。     

子宫肌瘤患者的子宫内膜病理特征分析

目的 探讨子宫肌瘤患者的子宫内膜病理特征及相关因素.方法 选取2007～2008年186例子宫肌瘤患者,分析其子宫内膜病理特征.结果 186例患者中有38例表现阴道不规则流血,单发肌瘤85例,多发肌瘤101例,子宫肌瘤变性27例,43例患者发生子宫内膜病变,包括子宫内膜息肉14例(7.53%)、子宫内膜单纯增生16例(8.61%)、复杂增生5例(2.69%)、非典型增生2例(1.08%)、子宫内膜癌6例(3.23%).结论 子宫肌瘤可同时合并子宫内膜病变及子宫内膜癌,子宫肌瘤单发或多发、子宫肌瘤变性等情况与子宫内膜病变无关.不规则阴道流血、绝经与子宫内膜病变及子宫内膜癌的发生有关.     

子宫内膜癌变过程中雌、孕激素受体的变化及与p53的关系

我们用免疫组化方法测定不同状态子宫内膜组织中癌基因 p5 3、增殖细胞核抗原 ( proliferativecellnuclearantigen ,PC NA)、雌激素受体 (estrogenreceptor ,ER)和孕激素受体 ( proges teronereceptor ,PR)的表达 ,分析 p5 3对子宫内膜癌组织ER、PR表达的影响 ,为临床诊治及预后判断提供参考。1　材料与方法1.1　材料　受检组织为我院 1997～ 1999年妇科手术标本共90例 ,其中子宫内膜腺癌 45例、子宫内膜癌前病变 15例 (包括腺瘤样增生过长和非典型增生 ,其中 4例伴灶性恶变 )、增生性子宫内膜 15例 (其中增生期内膜 5例、单纯性增生过…     

子宫内膜腺癌组织中cyclinD1、PCNA和Ki-67的表达

目的　探讨cyclinD1、PCNA和Ki 6 7在子宫内膜腺癌组织中的表达及其意义。 方法　采用免疫组化S P法检测正常增生期子宫内膜 10例、单纯性增生 30例、复杂性增生 30例、非典型增生 30例和子宫内膜腺癌 4 7例组织中cyclinD1、PCNA和Ki 6 7的表达。结果　cyclinD1在增生期子宫内膜组织中未见阳性表达 ,在单纯性增生、复杂性增生、非典型增生和子宫内膜腺癌组织中的阳性表达率分别为 13 3%、16 7%、30 0 %和 5 7 8%。非典型增生和子宫内膜腺癌组织阳性表达率高于增生期宫内膜、单纯性和复杂性增生 (P <0 0 5 ) ,cyclinD1蛋白表达与子宫内膜腺癌临床分期、肌层浸润和淋巴结转移呈正相关 (P<0 0 5 ) ,而与肿瘤的分化程度无关 (P >0 0 5 )。PCNA和Ki 6 7在非典型增生组标记指数 (LI)高于增生期宫内膜、单纯性和复杂性增生组 ,子宫内膜腺癌组高于非典型增生组 (P <0 0 5 ) ,PCNA和Ki 6 7LI与肿瘤的分化程度、临床分期、肌层浸润和淋巴结转移呈正相关 (P <0 0 5 )。PCNA和Ki 6 7在cyclinD1阳性表达组的LI高于阴性组 (P <0 0 5 )。结论　cyclinD1蛋白过度表达可能在子宫内膜癌的发生、发展中起重要作用 ,其作用途径可能是通过促进细胞增殖而实现的。     

子宫内膜非典型性增生鉴别要点及治疗

非典型性增生是病理学的名词，主要指上皮细胞异乎常态的增生，表现为增生的细胞大小不一，形态多样，核大而浓染，核浆比例增大，核分裂可增多但多呈正常核分裂像。细胞排列较乱，细胞层次增多，极向消失。但一般不见病理性核分裂；可发生于皮肤或粘膜表面的被覆上皮，也可发生于腺体上皮。一般认为，从正常细胞发展到肿瘤细胞，都要经历一个这样的过程，即：正常冥冥增生冥冥非典型增生冥冥原位癌冥冥浸润癌，而非典型增生则是从良性改变到恶性改变的中间站，是由量变到质变的关键点，因此，将非典型增生称之为癌前病变。非典型增生是癌前病变的形态学改变。增生的上皮细胞形态和结构出现一定程度的异型性，但还不足以诊断为癌。子宫内膜非典型性增生是子宫内膜增生的一种类型。子宫内膜增生有子宫内膜单纯性增生、子宫内膜复杂性增生、子宫内膜非典型性增生。子宫内膜非典型性增生和子宫内膜复杂性增生和子宫内膜单纯性增生有什么区别呢？此文我们就具体诊断子宫内膜非典型性增生来做具体阐述。     

Ki-67及ezrin在子宫内膜腺癌中的表达及意义

目的　探讨Ki 6 7及ezrin在子宫内膜癌中的表达及意义。方法　应用免疫组化方法检测Ki 6 7和ezrin在子宫内膜腺癌、非典型增生、子宫内膜增殖症及正常内膜中的表达 ;应用RT PCR技术对Ki 6 7 和ezrin mRNA在子宫内膜癌及正常内膜中的表达进行半定量分析。结果　Ki 6 7指数在子宫内膜癌、非典型增生及子宫内膜增殖症分别为 39.9± 6 .4、1 8.9± 1 4 .7、1 8.6± 1 5 .3,明显高于正常子宫内膜的 1 .1± 1 .6 7(P <0 .0 5 )。正常及子宫内膜增殖症的ezrin表达几乎全集中于细胞膜上 ,而子宫内膜癌及非典型增生的ezrin表达则为细胞浆内的弥漫性染色。在子宫内膜癌组织中 ,Ki 6 7mRNA表达为 0 .6 0 75± 0 .0 887,高于正常内膜组织的 0 .35 32± 0 .1 2 6 7。结论　Ki 6 7抗原过量表达与子宫内膜癌的发生及恶性程度密切相关 ;ezrin的着色部位对子宫内膜病变的性质有标识作用     

子宫内膜增生及内膜癌中PTEN、Ki-67蛋白的表达

目的　研究子宫内膜增生组织及内膜癌组织中PTEN、Ki 6 7蛋白的异常表达 ,探讨其与子宫内膜癌变的关系及作为早期癌变生物学标志的可能性。方法　应用免疫组化S P法对 12例正常增生期子宫内膜组织、4 0例子宫内膜增殖症组织、4 2例内膜腺癌组织中PTEN、Ki 6 7蛋白的表达进行研究。结果　在正常增生期子宫内膜、子宫内膜增殖症 (单纯增生、复杂型增生、不典型增生 )、子宫内膜腺癌组织中PTEN蛋白的阳性表达率呈递减趋势 ;Ki 6 7蛋白的阳性表达率呈递增趋势。等级相关分析结果显示PTEN、Ki 6 7表达异常与子宫内膜组织学分级均显著相关 (相关系数r分别为 - 0 5 4 1和 0 4 96 ,P值均<0 0 1)。子宫内膜癌与除不典型增生外的子宫内膜增殖症组织及正常增生期子宫内膜组织的PTEN、Ki 6 7蛋白表达差异有显著性 ,正常增生期子宫内膜、单纯增生与不典型增生组织的PTEN蛋白表达差异有显著性 ,不典型增生与单纯增生组织的Ki 6 7蛋白表达差异有显著性。PTEN、Ki 6 7蛋白表达存在负相关性 (r =- 0 4 2 8,P <0 0 1)。PTEN、Ki 6 7蛋白的表达与子宫内膜癌的手术分期、组织学分级、肌层浸润无关 (P >0 0 5 )。结论　PTEN、Ki 6 7蛋白的异常表达与子宫内膜的癌变过程相关 ,PTEN基因表达异常及细胞增殖异常与子宫内膜     

Expression of cyclin D1 in endometrial hyperplasia and endometrial carcinoma

This study investigates the role of cyclin D1 in 30 uterine surgical resection and endometrial biopsy specimens from 30 patients with simple hyperplasia (10 cases), complex hyperplasia (6 cases) and endometrial carcinoma (14 cases). Cyclin D1 immunohistochemistry was performed on 2-4 mm thick paraffin sections using labelled streptavidin biotin kit. Cyclin D1 expression was present in 2/6 (33%) cases of complex hyperplasia, 7/14 (50%) cases of endometrial carcinoma and none in simple hyperplasia. Difference in cyclin D1 immunopositivity in simple hyperplasia and endometrial carcinoma was statistically significant (p = 0.018) but the difference in cyclin D1 immunopositivity between complex hyperplasia and endometrial carcinoma was not statistically significant. Our study suggests that cyclin D1 over-expression may be an early event in endometrial carcinogensis. Since there was no difference in extent and intensity of cyclin D1 expression between complex hyperplasia and endometrial carcinoma, it appears that deregulation is maximal in complex hyperplasia.     

Oxidative stress in endometrial hyperplasia

OBJECTIVE: Reactive oxygen species seem to be involved in the onset and promotion of carcinogenesis. In 80% of cases of endometrial adenocarcinoma type I, a clear association exists with endometrial hyperplasia, which is considered a key factor in the endometrial oncological spectrum. The presence or absence of atypical cells determines oncological potential. This study explored the behavior of oxidative stress (catalase and malondialdehyde) in endometrial hyperplasia (with or without atypical cells) by comparing it with the oxidative stress existing in both the proliferative and secretory phases. DESIGN: Endometrial specimens from 55 women were used, 32 of which were histologically diagnosed as physiological (17 proliferative and 15 secretory endometria) and 23 as endometrial hyperplasia (18 nonatypical and 5 atypical endometrial hyperplasia). RESULTS: Significant differences were found in the malondialdehyde variable between the proliferative endometrium and the endometrium with atypical hyperplasia (P = 0.0208) and between both types of endometrial hyperplasia (P = 0.0441). The other comparisons were not statistically significant. No changes in catalase activity were observed. CONCLUSION: Our findings seem to suggest that the presence of atypical cells in endometrial hyperplasia induces a reduction in lipid peroxidation, which could permit survival and growth of these cells. This possible decrease in lipid peroxidation does not seem to be mediated by an increase in endometrial catalase activity.     

Differential diagnosis of endometrial hyperplasia and carcinoma by computerized image cytometry of cell proliferation, apoptosis and Bcl-2 expression.

BACKGROUND: The differential diagnosis between atypical endometrial hyperplasia and endometrial carcinoma is often difficult and based on controversial criteria. Cell kinetic parameters may be helpful. DESIGN: Cell proliferation, apoptosis and Bcl-2 expression were evaluated in benign endometrium, non atypical and atypical endometrial hyperplasia and endometrial carcinoma. The results were compared by one way analysis of variance and Bonferroni T tests. RESULTS: Cell proliferation was significantly higher (p < 0.01) in endometrial adenocarcinoma (25.6 percent) than in atypical hyperplasia (17.1 percent) and non-atypical hyperplasia (7.5 percent) of the endometrium. Apoptosis was observed in 12.3 percent of endometrial adenocarcinomas and less frequently in atypical hyperplasia (7.4 percent) and non-atypical hyperplasia of the endometrium (5.8 percent). Bcl-2 expression was significantly lower (p < 0.002) in endometrial adenocarcinoma (1.7 percent) than in atypical hyperplasia (4.2 percent) and non-atypical hyperplasia (5.3 percent) of the endometrium. In benign endometrium, cell proliferation and Bcl-2 expression were significantly higher during the proliferative phase while the rate of apoptosis was significantly higher during the secretory phase. CONCLUSIONS: Our data suggests that cell proliferation, apoptosis and Bcl-2 expression could be helpful when distinguishing endometrial carcinoma from non-atypical or atypical endometrial hyperplasia.     

Difficulties and mistakes in the diagnosis of atypical endometrial hyperplasia

687 endometrial biopsy specimens with morphological diagnosis "atypical endometrial hyperplasia" were examined by pathologists from the city cancer. The specimens were obtained from 32 hospitals of Saint Petersburg. They revealed atypical endometrial hyperplasia in 47 (6.8%) cases, endometrial adenocarcinoma in 54 (7.9%), typical hyperplasia in 211 (30.7%), polyp in 165 (24%), proliferative endometrium in 89 (13.0%), secretory endometrium in 80 (11.7%), and atrophic endometrium in 10 (1.4%). Thirty-one (4.5%) biopsy specimens failed to provide evidence. Also biopsy and surgery specimens (n = 78) were compared. Hysterectomy was performed in atypical endometrial hyperplasia. Comparison of the diagnoses revealed atypical endometrial hyperplasia in 14 (17.9%) cases, endometrial adenocarcinoma in 41 (52.7%), typical endometrial hyperplasia in 21 (26.9%), and polyp in 2 (2.5%).     

端粒酶逆转录酶和c-myc基因在子宫内膜样癌及子宫内膜增生中的表达

目的　探讨端粒酶逆转录酶 (hTERT)及c myc基因在子宫内膜增生及癌变过程中的作用、意义及二者相关性。方法　所用标本包括 14例子宫内膜单纯增生 ,8例复合增生 ,10例不典型增生 ,42例内膜样癌 ,用原位杂交法检测hTERT和c mycmRNA表达。结果　 (1)hTERT在子宫内膜单纯、复合、不典型增生病变和内膜样癌中阳性结果分别 2 / 14、4/ 8、8/ 10和 92 9% (3 9/ 42 ) ,前两组均为弱阳性表达 ,后两组多为中度和强阳性 ,统计分析表明不典型增生病变和内膜样癌中hTERT表达高于单纯和复合增生 (P <0 0 5)。c myc在子宫内膜单纯、复合、不典型增生病变和内膜样癌中阳性结果分别 3 / 14、1/ 8、5/ 10和 54 8% (2 3 / 42 ) ,后两组c myc阳性率显著高于前两组 (P <0 0 5) ;不典型增生病变的c myc阳性水平高于单纯及复合增生 (P <0 0 5)。(2 )hTERT阳性水平与内膜样癌分化相关(P <0 15) ;c myc阳性率随内膜样癌浸润深度增加而递增 (P <0 0 5)。 (3 )子宫内膜增生和内膜样癌各组中hTERT与c myc表达均不相关 (P >0 0 5)。结论　hTERT及c myc基因过表达与子宫内膜不典型增生及恶性转化相关 ,并与内膜样癌演进以及不良预后有关 ,但其两者表达之间无相关性     

Endometrial hyperplasia and the risk of progression to carcinoma

The primary presenting symptom of endometrial neoplasia is abnormal uterine bleeding, which typically prompts an endometrial biopsy to rule out carcinoma. Approximately 70% of women with abnormal uterine bleeding are diagnosed with benign findings and 15% are diagnosed with carcinoma. The remaining 15% receive a diagnosis of endometrial hyperplasia (EH), which includes a broad range of lesions, from mild, reversible proliferations to the immediate precursors of carcinoma. The widely used World Health Organization (WHO) system classifies EH according to four combinations of glandular crowding and nuclear atypia: simple (SH), complex (CH), simple atypical (SAH), or complex atypical hyperplasia (CAH), although the two forms of atypical hyperplasia (AH) are often collapsed into one category. Diagnoses of EH raise three issues. First, the low interobserver reproducibility—less than 50% in almost all studies—hinders the ability of WHO-based classification to effectively guide clinical management. Second, approximately 50% of women diagnosed with AH have concurrent carcinoma. Not surprisingly, most women with AH undergo hysterectomy as primary treatment, but non-surgical management can be effective. Third, data on progression risks for women with EH who retain their uterus are extremely limited. Emerging data indicate the long-term risk among women with SH or CH is less than 5%, but the risk among women with AH is approximately 30%. These data highlight priority areas for future research, such as increasing the diagnostic reproducibility of EH, improving the discrimination between AH and carcinoma, and identifying biomarkers to stratify risks or serve as indicators of response to clinical treatment.     

Nuclear and cytoplasmic bcl-2 expression in endometrial hyperplasia and adenocarcinoma

The bcl-2 proto-oncogene, which inhibits programmed cell death (apoptosis), has recently been found to be cyclically expressed in human endometrium. In order to investigate its role in endometrial hyperlasia and neoplasia, bcl-2 expression was studied in 25 cases of endometrial carcinoma and 20 cases of endometrial hyperplasia (eight simple, two complex, and ten atypical hyperplasias). Uniform intense cytoplasmic bcl-2 expression was found in all cases of non-atypical hyperplasia, and less strong positivity in eight out of ten cases of atypical hyperplasia. In well-differentiated carcinomas, nine out of ten showed weak to moderate bcl-2 expression, whereas six out of seven poorly differentiated carcinomas were bcl-2-negative. Moderately differentiated tumours were an intermediate group, with six out of eight being positive. Widespread localization of bcl-2 protein to the chromosomes of dividing cells was also demonstrated, regardless of cytoplasmic bcl-2 expression, with rare staining of interphase nuclei. Our findings suggest a role for bcl-2 in the natural history of endometrial neoplasia and studies are needed to determine its usefulness as a prognostic marker. The finding of bcl-2 localization to chromosomes has important implications for its mode and site of action.