无排卵型功血患者子宫内膜VEGF和雌、孕激素受体的表达

研究无排卵型功血患者子宫内膜血管内皮生长因子 (VEGF)、雌激素受体 (ER)和孕激素受体 (PR)的表达 ,探讨其与子宫内膜血管形成的关系 ,以求从蛋白水平阐明无排卵型功血的出血机制。采用免疫组化方法 ,检测VEGF、ER和PR在 2 0例正常增殖期和 6 0例无排卵型功血患者子宫内膜的表达。选用微血管密度标记物CD34,测定子宫内膜微血管密度 (MVD)。无排卵型功血患者单纯性增生和复合性增生子宫内膜腺上皮VEGF蛋白和MVD明显低于正常增殖期 (P <0 0 5和P <0 0 1 ) ;而单纯性增生和复合性增生子宫内膜腺上皮PR蛋白明显高于正常增殖期 (P <0 0 5和P <0 0 1 )。相关分析显示 ,子宫内膜腺上皮VEGF与MVD呈显著性正相关 (r =0 6 6 6 ,P <0 0 5 ) ;与腺上皮PR呈显著性负相关 (r=- 0 6 2 9,P <0 0 5 )。正常增殖期内膜与功血增殖期内膜比较 ,腺上皮VEGF和PR蛋白差异无显著性意义。首次指出病理表现为单纯性增生和复合性增生的无排卵型功血患者 ,其子宫异常出血与子宫内膜VEGF和PR的表达失调有关。PR间接作用于无排卵型功血子宫内膜腺上皮VEGF ,使后者分泌减少 ,微血管形成障碍 ,临床表现为子宫不规则出血     

血管紧张素Ⅱ1型受体和血管紧张素转化酶在子宫内膜癌中的表达及相关性

目的 检测血管紧张素Ⅱ1型受体(angiotensin Ⅱ type 1 receptor,AT1R)和血管紧张素转化酶(angiotensin converting enzyme,ACE)在子宫内膜癌中的表达情况,探讨AT1R和ACE在子宫内膜癌患者预后判断和临床治疗等方面的价值.方法 采用免疫组化EnVision法染色,观察AT1R、ACE、血管内皮生长因子(vascular endothelial growth factor,VEGF)和微血管密度(microvessel density,MVD)在18例正常子宫内膜、37例子宫内膜不典型增生和89例子宫内膜癌组织中的表达情况,分析AT1R和ACE与子宫内膜癌临床病理特征的关系,研究AT1R与VEGF和MVD的相关性.结果 从正常子宫内膜上皮到子宫内膜不典型增生再到子宫内膜癌,AT1R的表达逐步上调,ACE的表达逐步下调,差异均有显著性.子宫内膜癌中AT1R的表达与患者年龄、临床分期、子宫肌壁浸润深度和淋巴结转移状况等有关,且AT1R的表达与VEGF的表达和MVD计数正相关,而ACE的表达仅与淋巴结转移状况有关.结论 AT1R可能参与子宫内膜癌的发生、发展,AT1R表达上调可促进癌细胞生长和新生血管形成,与子宫内膜癌的预后有关,AT1R可能成为治疗子宫内膜癌的新靶点.ACE在子宫内膜癌中的表达低于正常内膜组织,其具体机制有待于进一步研究.     

EphA2及其配体在子宫内膜样腺癌中的表达及其与血管生成的关系

 目的： 探讨生促红素肝细胞受体A2 （EphA2）及其配体ephrin-A1在子宫内膜样腺癌组织中的表达及其与肿瘤血管生成的关系。方法： 利用免疫组织化学法检测56例子宫内膜样腺癌、20例子宫内膜增生过长、30例正常子宫内膜增殖期和30例分泌期组织中EphA2、ephrin-A1、雌激素受体（ER）和孕激素受体（PR）的表达,并采用CD34抗体标记微血管内皮细胞,计算微血管密度(MVD)。分析EphA2和ephrin-A1的表达与MVD之间的相关性及其与子宫内膜样腺癌临床病理特征的关系。结果： 子宫内膜样腺癌组织中EphA2和ephrin-A1的表达显著高于子宫内膜样增生过长及正常子宫内膜(P<0.05);EphA2和ephrin-A1表达水平及MVD值与子宫内膜样腺癌FIGO分期、肿瘤分化程度、肌层浸润深度、淋巴微血管浸润和孕激素受体表达有关(P<0.05);Spearman等级相关分析表明EphA2和ephrin-A1表达分别与MVD呈显著正相关(r=0.476,P<0.05;r=0.501,P<0.05)。结论： EphA2及其配体ephrin-A1在子宫内膜样腺癌中高表达,可能参与了肿瘤血管生成和孕激素抵抗。     

子宫内膜癌组织中生长抑素受体、VEGF的表达及其与血管形成的关系

目的 探讨生长抑素受体(somatostatin receptor,SSTR)、血管内皮生长因子(vascular endothelial growth factor,VEGF)在子宫内膜癌组织中的表达及其与肿瘤血管形成的关系.方法 应用免疫组织化学方法检测60例子宫内膜癌组织中SSTR各亚型、VEGF及CD34标记的微血管密度(microvessel denisity,MVD)的表达情况,探讨其与子宫内膜癌临床病理学特征及肿瘤血管形成的关系.结果 在60例子宫内膜癌组织中,SSTR各亚型(SSTR1、SSTR2、SSTR3、SSTR4及SSTR5)的阳性表达率分别为70.0 %,15.0 %,21.7 %,23.3 %及18.3 %;SSTR3、SSTR4在中高分化组表达阳性率明显高于低分化组(P＜0.05).VEGF的阳性表达率为83.3 %,VEGF在低分化组表达阳性率明显高于中高分化组、深肌层浸润组表达阳性率明显高于浅肌层浸润组、FIGO分期≥Ⅱ期组表达阳性率明显高于Ⅰ期组(P＜0.05).子宫内膜癌组MVD(44.85±15.78)明显高于正常子宫内膜组MVD(18.96±4.30)(P＜0.01).SSTR5的表达与VEGF呈负相关,VEGF阳性表达组子宫内膜癌组织MVD高于VEGF阴性组.结论 联合检测SSTR和VEGF对子宫内膜癌预后的评估有一定临床意义.生长抑素类似物(somatostatin analogs,SSTA)可能为子宫内膜癌的诊治提供新的靶点.     

Fhit、p53表达与子宫内膜癌发生和发展的相关性

目的　探讨正常子宫内膜、子宫内膜增殖症及内膜癌组织中Fhit、p53蛋白表达,以及与子宫内膜癌发生、发展的关 系。方法　应用免疫组化S P法检测37例正常子宫内膜组织、27例单纯型增生过长、28例复杂型增生过长、38例子宫内膜癌 组织中Fhit、p53蛋白的表达。结果　在正常子宫内膜(增生期、分泌期)、子宫内膜增殖症(单纯型增生过长、复杂型增生过 长、不典型增生)、子宫内膜腺癌组织中Fhit蛋白的阳性表达率依次递增,差异有显著性(χ2=33.726,P<0.005)。p53蛋白的 阳性表达率也依次递增,差异有显著性(χ2=58.474,P<0.005)。在腺瘤型增生过长、不典型增生及子宫内膜腺癌组织中Fhit (χ2=6.571,P=0.037)、p53(χ2=6.915,P=0.032)蛋白的阳性表达率依次递增,差异有显著性。Fisher精确概率检验显示不 同肌层浸润组Fhit(P=0.033)、p53(P=0.034)蛋白的表达差异有统计学意义,而在年龄、是否绝经、手术病理分期、组织学分 级组的表达无统计学意义(P>0.05)。Spearman等级相关分析显示Fhit、p53蛋白表达呈正相关(r=0.900,P<0.05)。在月 经期内膜的腺上皮细胞胞质中的Fhit蛋白阳性表达率为72.72%。结论　Fhit、p53蛋白的表达与子宫内膜癌的发生相关。 Fhit基因可能成为子宫内膜组织早期癌变的分子标记物。     

乙酰肝素酶在子宫内膜癌组织中的表达及血管生成、浸润的关系

目的探讨乙酰肝素酶（Heparanase，Hpa）在子宫内膜癌组织中的表达及预后关系。方法采用S—P免疫组织化学法检测Hpa和CD34蛋白在子宫内膜癌组织和正常子宫内膜组织中的表达，并结合病理学分型、组织学分级、微血管密度（MVD）和临床分期探讨其意义。结果子宫内膜癌Hpa蛋白的表达显著高于正常子宫内膜（P〈0．05），子宫内膜癌组织中Hpa蛋白的表达与子宫内膜癌组织血管生成、病理分型、分期有关（P〈0．05）。结论Hpa蛋白在子宫内膜癌中呈高表达，并与子宫内膜癌血管生成、病理特征有关，检测其表达以对判断子宫内膜癌的生物学行为提供指标。     

中介素在人子宫内膜腺癌中的表达及意义

目的检测中介素(Intermedin)在人子宫内膜腺癌组织中的表达,探讨其表达与子宫内膜腺癌临床病理参数以及微血管密度(MVD)的关系。方法应用免疫组化方法检测中介素在子宫内膜单纯性增生、子宫内膜不典型增生和子宫内膜腺癌组织中的表达,通过免疫组化SP法检测组织内微血管密度(MVD),比较中介素表达与肿瘤微血管密度的关系。结果中介素在子宫内膜腺癌中的表达高于子宫内膜单纯性增生及不典型增生中的表达;在子宫内膜腺癌中,中介素的表达与肿瘤的临床FIGO分期呈正相关(P=0.018),与肿瘤的肌层浸润呈正相关(P=0.0004)。中介素的表达与肿瘤的MVD呈正相关(P=0.002)。结论中介素在子宫内膜腺癌的发生发展过程中起到促进作用,并参与肿瘤血管生成。     

CD34及CD105两种微血管标记物在瘢痕微血管构筑中的比较

背景：在瘢痕微血管构筑研究中,目前尚无可靠的瘢痕新生血管标记物。CD34和CD105是目前常用来标记微血管密度的一种方法,但两者又有各自特点。 目的：比较CD34、CD105两种微血管标记物在病理性瘢痕微血管构筑方面的特征差异。 方法：采用免疫组化的方法检测人正常皮肤、非病理性瘢痕、增生性瘢痕和瘢痕疙瘩内CD34、CD105的表达,采用图像分析软件测量阳性染色的微血管的内径、表达面积并分析以CD34、CD105标记的微血管的形态、分布特征。 结果与结论：在所有标本内,CD34标记的微血管较为成熟,多表现为分支状、肝窦状及芽孢状,微血管内径平均值为(73.14±13.81) μm;CD105标记的微血管较为幼稚,多表现为圆形或镶嵌状,部分无管腔,微血管内径平均值为(27.91±5.86) μm。作为微血管标记物,CD105在标记瘢痕新生血管方面优于CD34,CD105可视作瘢痕新生血管可靠的标记物。     

子宫内膜癌中Rb2/P130、PTEN及Ki-67的表达及意义

目的 探讨正常子宫内膜、子宫内膜增殖症及内膜癌组织中Rb2/P130、PTEN及Ki-67的表达以及与子宫内膜癌发生的关系.方法 应用免疫组化SP法检测30例正常子宫内膜组织、32例单纯型增生过长、31例复杂型增生过长、36例不典型增生、64例子宫内膜癌组织中Rb2/P130、PTEN和Ki-67的表达.结果 Rb2/P130、PTEN蛋白在正常子宫内膜、单纯性增生过长、复杂型增生、不典犁增生、子官内膜癌组织中的阳性表达率依次递减,而Ki-67的阳性表达率依次递增,子宫内膜癌和不典型性增生中Rb2/P130、PTEN阳性表达率明显低于正常增生期子宫内膜和单纯性增生,差异均有显著性(P均<0.01),而Ki-67的阳性表达率明显高于正常增牛期子宫内膜和单纯性增生过长,差异均有显著性(P均<0.01).Rb2/P130、PTEN阳性表达缺失与组织学分级有关(P均<0.01)、与子宫肌层浸润程度无关,Rb2/P130阳性表达缺失与淋巴结转移无关,PTEN阳性表达缺失与淋巴结转移有关(P<0.05),而Ki-67阳性表达与组织学分级、临床分期及淋巴结转移有关(P<0.01,P<0.05,P<0.01),与子宫肌层浸润程度无关.Rb2/P130、PTEN蛋白表达与Ki-67呈负相关(P<0.003.P<0.000).结论 Rb2/P130、PTEN蛋白与Ki-67的异常表达与子宫内膜癌的发生相关,有可能成为子宫内膜组织早期癌变的有用标记物.     

子宫内膜病变组织中Artermin的表达及意义

目的 观察Artermin(ARTN)在子宫内膜病变组织中的表达及其临床意义.方法 建立组织微阵列平台,应用免疫组化SP法检测38例正常子宫内膜、20例子宫内膜简单型增生、20例子宫内膜复杂型增生和47例子宫内膜样腺癌组织中ARTN蛋白的表达.结果 子宫内膜样腺癌中ARTN的阳性率为83.0%,明显高于正常子宫内膜、子宫内膜简单型增生和复杂型增生(P<0.01);子宫内膜样腺癌中ARTN的表达与肿瘤组织学分级、肿瘤子宫肌层浸润均有相关性(P<0.01,P<0.05).结论 子宫内膜样腺癌中ARTN的表达失调,其可能参与子宫内膜癌的发生、发展.     

Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas

Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours.     

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。     

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma

Endoglin (CD105), a member of transforming growth factor beta1 receptor complex, has been shown to be a more useful marker to identify tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor (VEGF) expression as possible prognostic markers in esophageal adenocarcinoma. Surgical specimens from 75 patients with esophageal adenocarcinoma treated with esophagectomy were immunostained for endoglin, CD31, and VEGF. We also included 10 cases of Barrett's esophagus with high-grade dysplasia and 10 cases with Barrett's esophagus low-grade dysplasia. Positively stained microvessels (MVs) were counted in hot spots at magnification of x400. Results were expressed as the highest number of MV identified. For VEGF, intensity of staining was scored on 3-tiered scale. Endoglin demonstrated significantly more vessels than the CD31 (mean, 28.9 +/- 13.2 versus 19.0 +/- 9.4, P < .001). Both endoglin and CD31 MV counts showed significant correlation with stage of the disease (r = 0.59, P < .001; r = 0.52, P < .001, respectively) and patient survival (log rank P < .01). Only endoglin MV count was significantly correlated with the presence of angiolymphatic invasion (r = 0.34, P < .05) and lymph node (LN) metastases (r = 0.48, P < .001). Univariate analysis showed that endoglin MV count is an independent prognostic factor. Endoglin showed a significant increase in MV count in Barrett's esophagus with high-grade dysplasia when compared with Barrett's esophagus low-grade dysplasia (P < .01), whereas CD31 did not show any significant difference. VEGF was expressed in 48 (64%) of 75 cases of adenocarcinoma and was significantly correlated with angiolymphatic invasion, LN metastases, and survival. In conclusion, endoglin is a specific and sensitive marker for tumor angiogenesis. Endoglin staining also showed prognostic significance with positive correlation with the presence of angiolymphatic invasion, LN metastases, tumor stage, and survival.     

Comparative evaluation of microvessel density determined by CD34 or CD105 in benign and malignant gastric lesions

Microvessel density (MVD) is regarded as a surrogate marker for angiogenesis and has been used for tumor prognosis. In this study, MVD was identified immunohistochemically by monoclonal antibodies against CD105 and CD34 in the tissues representing gastric carcinoma, chronic gastritis, and hyperplastic polyps, and the results were correlated with clinicopathologic features. The expression of CD105 in the microvessels within benign lesions was barely visible, and MVD was markedly lower than that determined by CD34. CD34 was strongly expressed in the microvessels within hyperplastic polyps and tissues with gastritis. In gastric carcinoma, CD105 expression in microvessels was as high as the MVD, compared with benign lesions. CD105 stained well-formed mature and newly formed immature vessels within the cancer mass. Correlation analysis showed that MVD determined by CD105 correlated with blood vessel invasion, distant metastasis, and formation of ascites. Survival analysis demonstrated an inverse correlation between MVD count and overall survival: patients with MVD counts of 32 or higher survived for a much shorter time than those with counts lower than 32. Multivariate analysis confirmed that MVD determined by CD105 was an independent prognostic factor for survival. Microvessel density determined by CD34 inversely correlated with overall survival, but it did not correlate with other clinicopathologic parameters except formation of ascites. In conclusion, CD34 was universally expressed in blood vessels within benign and malignant tissues, whereas CD105 expression was minimal in benign tissues but stronger in gastric carcinoma. These data suggest that both CD105 and CD34 could be used for quantification of angiogenesis, but preference should be given to CD105 in the evaluation of prognosis in gastric carcinoma.     

Angiogenesis in craniopharyngiomas: Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin

Craniopharyngiomas are benign tumors of the sellar region generally associated with endocrine abnormality and often locally aggressive. Several studies have demonstrated that angiogenesis or neovascularization plays an important role in tumoral growth. The microvascular density (MVD) of craniopharyngiomas was determined in tumor tissue samples from a reference neurosurgery center located in southern Brazil using immunohistochemical methods for two endothelial markers, CD34 and CD105 (endoglin). In addition, tissue expression was determined for an angiogenesis stimulatory factor and for one of its inhibitors, the vascular endothelial growth factor (VEGF) and endostatin, respectively. Endothelial cell immunoreactivity for CD34 and CD105 was observed scattered within the stroma. MVD determined using CD105 antigen was significantly lower than the results obtained by using CD34 antigen. There was no association between the two endothelial markers and tumor extension. The epithelial component showed different degrees of immunoreactivity for VEGF and endostatin in all samples analyzed. We were not able to establish a relationship between angiogenesis in craniopharyngiomas and tumor extension with the endothelial markers used in this study. The investigated vascularization stimulatory and inhibitory factors showed no relation with MVD. We believe that CD105 antigen can be a more specific endothelial marker for tumor angiogenesis than CD34 antigen.     

Significance of hormone receptor status and tumor vessels in normal, hyperplastic and neoplastic endometrium

The aims of this study were to identity the roles of tumor vessels and hormone receptor status in normal, hyperplastic, and neoplastic endometrium, and to explore their relationships with other prognostic factors of endometrial adenocarcinoma. Endometrial curettage specimens of proliferative phase and secretory phase endometrium, simple hyperplasia with or without atypia, complex hyperplasia with or without atypia, and grade 1 adenocarcinoma were examined for estrogen receptor alpha (ER alpha), progesterone receptor (PgR), Ki-67 labeling index (LI), cyclin D1, microvessel density (MVD), and area of venules (AV) using an immunoperoxidase method. The results showed high levels of ER alpha in complex hyperplasia, and high levels of PgR in simple hyperplasia without atypia. Expression of ER alpha in the endometrium decreased in a stepwise manner from complex hyperplasia without atypia to grade 1 adenocarcinoma. Expression of PgR in the endometrium decreased in a stepwise manner from simple hyperplasia without atypia to grade 1 adenocarcinoma. In contrast, the expressions of Ki-67 LI, cyclin D1, MVD and AV in the endometrium increased in a stepwise manner from normal, simple or complex hyperplasia with or without atypia to grade 1 adenocarcinoma. These changes may become irreversible on progression from simple or complex hyperplasia to neoplasia.     

β-catenin、Glut-1和PTEN蛋白在子宫内膜样腺癌发生过程中的表达及意义

目的 通过分析子宫内膜上皮内瘤变(EIN)诊断、分类与子宫内膜增生WHO(2003)分类的关系,探讨β-catenin、Glut-1和PTEN蛋白在子宫内膜样腺癌发生过程中的表达及其意义.方法 根据EIN诊断及分类标准,对83例子宫内膜增生病例进行再分类.采用免疫组织化学SP法,对10例增殖期子宫内膜、83例子宫内膜增生及24例子宫内膜样腺癌组织中β-catenin、Glut-1及PTEN蛋白的表达进行检测.结果 (1)83例子宫内膜增生病例中共检出24例EIN病例,总检出率为28.9%(24/83).24例EIN病例中,来自复杂型不典型性增生16例(66.7%,16/24),但EIN的检出率与不典型增生的分级无明显关系(P＞0.05).(2)β-catenin蛋白在增殖期子宫内膜中呈正常表达,良性子宫内膜增生的异常表达率为10.2%(6/59),而EIN和子宫内膜样腺癌的异常表达率(50%,12/24;66.7%,16/24)分别明显高于良性子宫内膜增生(P＜0.01),但二者间的异常表达率差异无统计学意义(P＞0.05).(3)Glut-1蛋白在增殖期子宫内膜、良性子宫内膜增生组织中均呈低表达,而在EIN和子宫内膜样腺癌中的高表达率分别为58.3%(14/24)和70.8%(17/24),均显著高于增殖期子宫内膜及良性子宫内膜增生(P＜0.01),但二者高表达率间差异无统计学意义(P＞0.05).(4)PTEN蛋白在EIN病例中的失表达率(37.5%,9/24)与子宫内膜样腺癌(62.5%,15/24)、增殖期子宫内膜(2/10)及良性子宫内膜增生(28.8%,17/59)比较差异均无统计学意义(P＞0.05),但子宫内膜样腺癌的失表达率则明显高于增殖期子宫内膜及良性子宫内膜增生病例,其差异均具有统计学意义(P＜0.05).结论 β-catenin蛋白的异常表达和Glut-1蛋白高表达是子宫内膜样腺癌发生过程中的早期事件,二者在区别良性子宫内膜增生、EIN和子宫内膜样腺癌中可能是有用的免疫标志物.PTEN蛋白失表达是子宫内膜样腺癌发生过程中的极早期事件,但将其作为EIN病变的诊断性标志物并不恰当.     

Expression of hyaluronic acid and its receptors, CD44s and CD44v6, in normal, hyperplastic, and neoplastic endometrium

The interaction between epithelial tumor cells and their surrounding stroma is important in tumor progression and metastasis. This is accomplished through a number of transmembrane receptors that interact with stromal extracellular matrix molecules. One of these receptors, CD44, binds to extracellular matrix component hyaluronic acid (HA). The purpose of this study was to evaluate the significance of HA, CD44s, and CD44v6 in benign, hyperplastic, atypical, and malignant endometrial epithelia. Archival paraffin-embedded cell blocks from proliferative endometrium (n = 11), secretory endometrium (n = 12), simple hyperplasia (n = 13), complex hyperplasia without atypia (n = 9), complex hyperplasia with atypia (n = 17), and adenocarcinoma (n = 21) were stained for HA, CD44s, and CD44v6. HA was detected throughout the normal menstrual cycle but was more intense during the secretory phase. Only during the secretory phase was CD44s expressed in the stromal cells in 11 cases (92%), whereas CD44v6 was detected in glandular epithelium in 9 (75%). CD44s was expressed in the glandular epithelium in 2 (15%) cases of simple hyperplasia, 4 (44%) of complex hyperplasia without atypia, 14 (82%) of complex hyperplasia with atypia, and in 16 (76%) of adenocarcinoma. CD44v6 was expressed in the glandular epithelium in 1 (11%) case of complex hyperplasia without atypia, 17 (100%) cases of complex hyperplasia with atypia, and in 18 (86%) cases of adenocarcinoma, but in none of the cases of simple hyperplasia. The endometrial stromal cells expressed CD44v6 in 1 (8%) case of simple hyperplasia, 6 (67%) of complex hyperplasia without atypia, 8 (47%) of complex hyperplasia with atypia, and in 3 (14%) of adenocarcinoma. We concluded that in the normal menstrual cycle, the timing of peak staining of HA and CD44s in the stroma and the up-regulation of CD44v6 in secretory glands are coincident with the period in which the endometrium is most receptive to embryo implantation. HA is more abundant in the stroma adjacent to the tumor, suggesting that interactions between tumor cells and stromal HA promote tumorigenesis. With progression from hyperplasia and with increasing atypia to adenocarcinoma, levels of stromal HA, glandular CD44v6, and glandular and stromal CD44s all increase. Thus, HA and CD44 are both involved in the development and progression of endometrial cancer.