子宫内膜癌组织雌激素及孕激素受体的测定及其临床意义

目的：探讨子宫内膜癌组织雌激素受体（ＥＲ）和孕激素受体（ＰＲ）与临床病理特征的关系。方法：用葡聚糖－活性碳吸附法（ＤＣＣ法）对７０例子宫内膜癌原发病灶组织进行ＥＲ及ＰＲ测定，同时用免疫组化法对其中３０例的石蜡标本进行了ＥＲ及ＰＲ的检测。结果：ＤＣＣ法检测ＥＲ及ＰＲ的阳性率均为７７．１％，免疫组化法均为８３．３％。两种测定方法比较，ＥＲ与ＰＲ的总符合率分别为８３．３％和８６．７％。而免疫组化法可在ＤＣＣ法基础上进一步明确组织来源。ＥＲ及ＰＲ水平与组织学分级呈负相关。组织类型中，腺癌（包括乳头状腺癌）与腺棘癌的ＥＲ及ＰＲ水平高于其它癌。ＥＲ水平与肥胖呈正相关。结论：ＥＲ及ＰＲ水平与组织学分级、组织学类型均反映了子宫内膜癌的生物学行为，ＥＲ及ＰＲ的测定对估计预后和临床选择内分泌治疗具有重要意义。     

子宫颈癌放射治疗后发生子宫内膜癌的临床观察

目的了解宫颈癌放射治疗（放疗）后发生子宫内膜癌的临床特点。方法对２７例宫颈癌放疗后发生的子宫内膜癌的临床资料及雌激素受体（ＥＲ）、孕激素受体（ＰＲ）状态进行回顾性研究。结果宫颈癌放疗后子宫内膜癌的发生率为０．１９％。发病年龄平均为６３岁;接受放疗至确诊子宫内膜癌的时间平均为１５．６年;晚期患者占５１．９％,较一般子宫内膜癌明显高。ＥＲ、ＰＲ的表达率低,仅为１１．８％（２／１７）。５例Ｉ期子宫内膜癌均发生于接受放射剂量较低的宫角及宫底部。２７例中,１９例接受手术治疗,３年、５年的生存率仅为５６．８％及３７．８％。结论盆腔放疗后子宫内膜癌的发生率较其自然发生率为高,晚期患者比例大,ＥＲ、ＰＲ表达率低,治疗应以手术为主,预后较一般子宫内膜癌差     

女性生殖系统恶性肿瘤组织胞浆雌激素及孕激素受体的研究

应用葡聚糖－活性炭单点饱和分析法测定３４４例子宫内膜癌，１７７例子宫颈癌，２８９例卵巢恶性肿瘤，１０例外阴癌及４例输卵管癌组织胞浆的雌激素受体（ＥＲ）和孕激素受体（ＰＲ）含量。结果：ＬＲ及ＰＲ均量从高到低均依次为子宫内膜癌，卵巢恶性肿瘤及子宫颈癌。并探讨生殖系统不同恶性肿瘤组织胞浆ＥＲ和ＰＲ阳性率与患者绝经前后、肿瘤分化程度、临床期别及其预后之间的关系。提示：ＥＲ和ＰＲ含量对指导肿瘤患者术后内分泌治疗及判断预后有一定价值。     

子宫腺肌病深肌层异位内膜性激素及性激素受体测定的临床意义

选择子宫腺肌病住院手术病人４５例，采用ＡＢＣ免疫组化法测定石蜡固定包埋的深肌层异位内膜标本中雌二醇（Ｅ２）、孕激素（Ｐ）、睾酮（Ｔ）、雌激素受体（ＥＲ）、孕激素受体（ＰＲ）、雄激素受体（ＡＲ）。另取１７份增生期原位内膜作对照，分析性激素及性激素受体与临床表现的关系。研究发现子宫深肌层异位内膜有Ｅ２、Ｐ、Ｔ、ＥＲ、ＰＲ、ＡＲ阳性细胞存在，其中ＥＲ、ＡＲ阳性表达率显著高于原位内膜。但性激素及性激素受体的阳性率与子宫腺肌病的临床症状、病程和子宫体积无明显关系。提示：子宫腺肌病的发生、发展除了与雌激素有关外，还与孕激素、雄激素有关，同时应用抑制多种受体的药物可能是治疗子宫腺肌病的途径之一。     

过期妊娠胎盘等部位雌,孕激素受体水平的测定

采用荧光激素结合法，分别对３０例过期妊娠（过期妊娠组）和２７例足月妊娠妇女（对照组）有关的靶组织（胎盘、胎膜、子宫胎盘床和子宫下段肌层）的雌激素受体（ＥＲ）和孕激素受体（ＰＲ）进行了定性和定量分析。结果：过期妊娠组子宫胎盘床及胎膜ＥＲ水平较对照组明显减少，而ＰＲ却无明显差异；过期妊娠组各靶组织内ＥＲ与ＰＲ的比值（ＥＲ／ＰＲ）都明显低于对照组；各靶组织ＥＲ与ＰＲ水平呈明显的正相关；有宫缩者子这吕下段     

子宫腺肌病的激素受体免疫组织化学分析

对２４例子宫腺肌病病灶内腺上皮和２０例对照病例的子宫内膜激素受体行免疫组织化学分析，以研究正常子宫内膜与子宫腺肌病病灶内的腺上皮雌激素受体（ＥＲ）、孕激素受体（ＰＲ）、雄激素受体（ＡＲ）、卵泡刺激素受体（ＦＳＨ－Ｒ）、黄体生成素受体（ＬＨ－Ｒ）和垂体泌乳素受体（ＰＲＬ－Ｒ）的表达。结果：子宫腺肌病病灶内的腺上皮ＬＨ－Ｒ、ＰＲＬ－Ｒ、ＰＲ和ＡＲ的水平明显高于正常子宫内膜腺上皮。     

子宫腺肌病患者雄激素治疗前,后子宫内膜中雌,孕激素受体及表 …

目的 搪塞雌激素受体（ＥＲ）、孕激素受体（ＰＲ）、表皮生长因子受体（ＥＧＦＲ）及生长激素（ＧＨ）在子宫腺肌病中的表达及雄激素治疗疗效的关系。方法 对３０例子宫腺肌病患者（组１）及２４例合并肌瘤的子宫腺肌病患者（组２）的手术标本,应用免疫边霉亲合素－生物素化过氧化物酶复合物法测定ＥＲ、ＰＲ、ＥＧＦＲ及ＧＨ;另应用相同方法对２４例术前应用甲基睾丸素治疗的子宫腺肌瘤患者（组３）测定ＥＲ、ＰＲ、并进行比较     

Norplant皮下埋植后子宫内膜形态和雌、孕激素受体含量的变化

目的探讨Ｎｏｒｐｌａｎｔ皮下埋植后子宫内膜形态和雌、孕激素受体（ＥＲ、ＰＲ）含量的变化与子宫异常出血的关系。方法应用免疫组化、ＷｅｓｔｅｒｎＢｌｏｔ和原位杂交技术结合计算机图像分析,观察１６例Ｎｏｒｐｌａｎｔ皮下埋植后和２３例正常周期的内膜的形态学改变、细胞增殖状态及ＥＲ、ＰＲ蛋白及其ｍＲＮＡ的表达。结果埋植Ｎｏｒｐｌａｎｔ后,内膜ＤＮＡ含量降低;螺旋动脉数量减少,腺体的构成比例降低;腺体构成比例与雌二醇（Ｅ２）水平呈正相关,与子宫异常出血呈负相关,与年龄和体重无相关性,随使用期延长,腺体构成比增加。埋植后,内膜ＥＲ含量低于月经周期各期水平,但ＰＲ含量相当于或高于月经周期最高水平。ＥＲ、ＰＲｍＲＮＡ表达减弱,以ＥＲｍＲＮＡ表达降低更明显。结论内膜腺体和螺旋动脉再生修复不良和ＥＲ、ＰＲ表达异常,可能是Ｎｏｒｐｌａｎｔ致子宫异常出血的病理学基础     

子宫肌瘤与肌肉组织雌孕激素受体含量与月经周期及子 …

应用放射受体分析法测定４０例子宫肌瘤患者子宫肌瘤、肌肉组织雌激素受体（ＥＲ）、孕激素受体（ＰＲ）的含量，月经周期根据月经史经子宫内膜组织相来判断，比较两种组织ＥＲ、ＰＲ含量与月经周期及子宫内膜组织相的关系。结果：子宫肌瘤组织的ＥＲ、ＰＲ含量高于同一子宫正常肌层的含量（Ｐ〈０．０５）；子宫肌瘤与肌肉两种组织中ＥＲ含量在子宫内膜增殖期高于分泌期（Ｐ〈０．０２５，Ｐ〈０．０５），ＰＲ含量分泌期高于增殖期     

多囊卵巢综合征患者子宫内膜病理改变及雌,孕激素受体测定

目的观察多囊卵巢卵巢综合征（ＰＣＯＳ）患者子宫内膜病理改变及雌激素受体（ＥＲ）、孕激素受体（ＰＲ）改变。方法对３９例ＰＣＯＳ患者进行子宫内膜病理检查,采用免疫组化方法测定子宫内膜ＥＲ及ＰＲ,并以正常妇女作为对照。结果３４例（８７．２％）ＰＣＯＳ患者子宫内膜呈无排卵型,内膜增殖症发生率为５１．３％（２０／３９）,内膜腺体发育不同步为３５．９％（１４／３９）,内膜间质反应不良为４６．２％（１８／３９）。ＰＣＯＳ患者子宫内膜增殖期ＥＲ、ＰＲ较正常妇女增多（Ｐ＜０．０５）,内膜增殖症者间质ＰＲ减少（Ｐ＜０．０５）且分布不均匀。结论ＰＣＯＳ患者子宫内膜的病理改变和局部ＥＲ、ＰＲ减少或缺乏,可能是不孕的原因之一。     

Microsatellite instability in endometrial cancer: relation to histological subtypes.

Fifty-one endometrial cancers were analyzed with regard to whether or how microsatellite instability (MI) was associated with the development of different types of endometrial malignant neoplasms. We investigated 6 loci previously reported as informative for colorectal cancer and a group of 8 loci located on 6q. Replication error (RER+) phenotype was detected in 10 of 51 (19.6%) endometrial cancers (ECs), all but one of which showed endometrioid differentiation. On the contrary, the RER+ phenotype was not detected in serous carcinomas and malignant mixed Müllerian tumors. MI was present in both early and advanced stage ECs. No correlation was found between age, grade, stage, familial pattern, mitotic index, and the RER+ phenotype of ECs. Only 1 of 8 endometrial carcinomas showing MI was associated with mutant p53 expression, while the majority of RER+ tumors were positive for estrogen and progesterone receptors. Our findings suggest that MI plays an early role in endometrial tumorigenesis and is significantly correlated with adenocarcinomas showing endometrioid features (EAs). The frequent involvement of the telomeric region of chromosome 6 in the MI of EA is an indication that this region may be crucial in the process of EA tumorigenesis.     

卵巢上皮性肿瘤雌孕激素受体的单克隆抗体免疫组化研究

利用抗雌激素受体（ＥＲ）和孕激素受体（ＰＲ）的两种单克隆抗体对３１例卵巢上皮性肿瘤新鲜冰冻标本进行ＡＢＣ法测定，ＥＲ、ＰＲ的阳性表达率分别为４５．２％和４８．４％，恶性肿瘤ＥＲ的含量高于良性者，ＰＲ在良、恶性肿瘤间未见有明显差异。提示：部分卵巢上皮性肿瘤属于激素依赖性肿瘤，对晚期卵巢癌可试用激素疗法。ＥＲ、ＰＲ在宫内膜样癌和浆液性癌的含量高于其它类型上皮性肿瘤，高分化者受体阳性率及含量高于低分化者；ＥＲ或ＰＲＦ阳性者预后好于阴性者，二者具独立的预后因素，且ＥＲ、ＰＲ双阳性者预后比ＥＲ阳性、ＰＲ阴性或ＥＲ阴性、ＰＲ阳性者好。     

子宫内膜癌组织中环氧化酶-2与雌、孕激素受体的表达及相关性研究

目的:探讨子宫内膜癌组织中环氧化酶-2(COX-2)、雌激素受体(ER)和孕激素受体(PR)的表达及相关性。方法:应用免疫组化SP法检测56例子宫内膜癌中COX-2、ER和PR的表达。结果:COX-2在子宫内膜癌中的表达率随病理分级的增高而升高,与患者年龄、临床分期和淋巴结转移情况无关。ER和PR在子宫内膜癌的表达与临床分期及病理分级、淋巴结转移有关,表达率随临床分期增加、病理分级增高及淋巴结转移而降低。COX-2的表达与ER和PR无关。结论:COX-2可能介导不同的生物学途径,可以联合内分泌药物与特异性COX-2抑制剂治疗转移或复发的子宫内膜癌。     

Dualistic model of molecular pathogenesis in endometrial carcinoma

Sporadic endometrial carcinoma can be divided into two biologically and clinically distinctive subtypes of which one is estrogen-related (type I), the other estrogen-unrelated (type II). Type I carcinomas occur at younger age, express estrogen (ER) and progesterone receptors (PR), are frequently associated with endometrial hyperplasia and show a good prognosis. Type II carcinomas occur at older age, are negative for ER and PR, arise in the background of atrophic endometrium and show poor prognosis. Histologically, endometrioid carcinomas correspond to type I carcinomas whereas serous carcinoma is the prototype of type II carcinomas. Endometrioid and serous carcinomas are significantly different with respect to their molecular changes. Endometrioid carcinomas frequently show microsatellite instability (MIN), PTEN and K-ras mutation but infrequently p53 mutations, loss of p16 expression and her2/neu amplification, respectively. In contrast, serous carcinomas show a high frequency of p53 mutations and often loss of p16 expression whereas MIN and PTEN and K-ras mutations are uncommon. Familial endometrial carcinoma associated with HNPCC occur about two decades earlier than sporadic carcinomas, show endometrioid histology and are frequently MIN positiv due to germline mutations of mismatch repair genes (mostly MLH1 and MSH2). During the progression of endometrioid carcinoma PTEN mutations and MIN are considered early changes since they are present in a high frequency in atypical endometrial hyperplasia whereas p53 mutations, loss of p16 expression and her2/neu amplification are considered late events since they are predominantly found in poorly differentiated tumors. In contrast, p53 mutations are considered an early event in the pathogenesis of serous carcinoma occurring already in its putative precursor endometrial intraepithelial carcinoma (EIC). The future research will focus, besides the discovery of new relevant genes, on the interaction of known genes as well as their clinical relevance.     

Clinicopathologic and immunohistochemical features and microsatellite status of endometrial cancer of the uterine isthmus.

To clarify the clinicopathologic, molecular, and immunohistochemical characteristics of uterine isthmic endometrial cancer (UIE), we examined 13 cases of UIE and compared them with 33 cases of endometrial cancer of the uterine corpus (UCE) with respect to clinicopathologic factors, the expression of p53, the estrogen receptor (ER) and the progesterone receptor (PR) status, DNA ploidy, and microsatellite instability (MSI). Five (38.4%) of the UIE patients had stage I, two (15.4%) had stage II, and six (46.2%) had stage III disease (FIGO 1988). Myometrial invasion was confirmed in 92.3% of the UIE patients, and these patients had a higher (p < 0.05) frequency of > 50% myometrial invasion (46.2%) than the patients with UCE (15.2%). Moreover, the UIE patients had a higher frequency of positive peritoneal cytology (p < 0.05) and pelvic lymph node metastases (p < 0.05). No UIE tumors exhibited MSI, and the tumors in these patients had a higher expression of p53 (p < 0.01), a lower expression of ER (p < 0.05) and PR (p < 0.05), and a higher frequency of DNA aneuploidy (p < 0.01) than the UCE tumors. These findings suggest that the UIE is clearly different from UCE in the clinicopathologic, immunohistochemical features, and microsatellite status.     

Molecular differences between RER+ and RER– sporadic endometrial carcinomas in a large population-based series

Studies, to date, have suggested that there are distinct molecular differences between microsatellite stable (RER(-)) and unstable (RER(+)) solid tumors, such as colorectal carcinoma. We investigated a range of molecular events including mutation frequency of K-ras, microsatellite instability within the coding region of TGF-beta RII, BAX, and IGF-IIR, loss of expression of p53, hMLH1, hMSH2, hMSH6, and PTEN, and methylation of hMLH1, hMSH2, and PTEN within a large population-based series of sporadic endometrial carcinomas to establish whether there are distinct differences between replication error repair (RER(+)) and RER(-) cases. RER(+) endometrial carcinomas tended to be diploid with normal p53 expression, compared with RER(-) cases. Mutations in TGF-beta RII, IGF-IIR, and BAX were rare, but there was a strong association between mutation and RER(+) status. Methylation and loss of hMLH1 expression were significantly more common in RER(+) cases, as was methylation of PTEN. K-ras mutations were equally frequent in RER(+) and RER(-) cases. Despite the absence of distinct clinicopathological differences between RER(+) and RER(-) cases in this series of sporadic endometrial carcinomas, our results confirm that there are molecular differences between RER(+) and RER(-) cases, but the molecular events occurring in RER(+) endometrial carcinomas differ from those seen in RER(+) colorectal carcinomas.     

Immunohistochemical bcl-2 expression, p53 overexpression, PR and ER status in endometrial carcinoma and survival outcomes

Immunohistochemical expression of bcl-2, p53, PR and ER in cases with endometrial carcinomas arrayed on a tissue microarray (TMA) was tested and correlated with clinicopathologic features, overall survival (OS), cancer-related survival (CRS) and disease-free survival (DFS). Seventy-seven patients with endometrial cancer were reviewed. Slides were evaluated by two pathologists blinded to patient clinical characteristics and survival data. Mean age of patients was 62.5 years (range 35-80), median follow up 60 months (range 9-120). Seventy-nine percent of patients were FIGO Stage I; 39% of the cases showed bcl-2 cytoplasmic staining and its expression was significantly correlated with low-grade tumor differentiation and age < or = 60 years. Nuclear p53 overexpression was detected in 23.4% of the cases and was significantly correlated with advanced stages (IIB-IV), non-endometrioid histology, nodal metastasis and advanced age (> 60 years). PR and ER were positive in 63.6% and 30% of the cases, respectively. Analysis of p53 overexpression and bcl-2 expression in relationship with PR and ER status showed a direct correlation between bcl-2 expression and PR positivity (p = 0.001). In a multivariate analysis FIGO staging was the only clinicopathologic parameter independently correlated with DFS. In conclusion p53 overexpression was directly associated with unfavorable clinicopathologic factors such as advanced stage, histologic subtype, advanced patient age and nodal metastasis. Bcl-2 expression was related with younger age, favorable grade and PR expression by tumor cells. Patient survival was not related to the tested biomarkers.     

Prognostic Significance of Progesterone Receptor Immunohistochemistry in Endometrial Carcinoma

Objective.The aim of this study was to evaluate the prognostic significance of steroid hormone receptors in endometrial carcinoma using immunohistochemical staining for progesterone receptor (PR) and estrogen receptor (ER).Methods.We evaluated the correlation between PR/ER immunohistochemistry and age, clinical stage, tumor grade, myometrial tumor invasion, and disease-free survival in a series of 92 cases of endometrioid adenocarcinoma.Results.Fifty (54.4%) endometrial carcinomas were PR-positive and 44 (47.8%) were ER-positive. PR immunohistochemistry of endometrial carcinoma was statistically correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (I, II vs III, IV,P= 0.001), FIGO grade (G1 vs G2 vs G3,P= 0.007), the depth of myometrial tumor invasion (1/2 vs >1/2,P= 0.006), and disease-free survival (living vs dead,P= 0.0025). In contrast, ER immunohistochemistry had significant correlations with the depth of myometrial tumor invasion (P= 0.026) and disease-free survival (P= 0.032). Multivariate analysis of PR/ER immunohistochemistry, stage, grade, and myometrial invasion showed that the PR immunohistochemistry was a significant prognostic factor for survival (P= 0.026).Conclusion.PR/ER immunohistochemistry was significantly related to survival and PR immunohistochemistry appeared to be the most reliable means for predicting survival in endometrioid adenocarcinoma of the endometrium, independent of other clinicopathological parameters.     

Genetic analysis of familial and multiple malignancies of endometrial cancer.

The presence of the positive replication errors (RER) phenotype in familial and multiple primary malignancies of endometrial cancer, and its association with a poor prognosis was examined. We analyzed 40 endometrial cancers for RER. Eight endometrial cancers with the RER(+) phenotype at multiple microsatellite loci were detected. The presence of the RER(+) phenotype was higher than in non-familial malignancies. None of the eight cases with the RER(+) phenotype involved multiple primary malignancies; however these patients had shorter survival times. In this study, we suggest that RER examination in endometrial cancer may be useful for establishing a diagnosis of a familial malignancy, and for predicting a poor prognosis.