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     

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.     

绝经后妇女子宫内膜增厚的临床意义探讨

目的 评估对绝经后经阴道超声诊断子宫内膜≥5mm的妇女病理活检的价值,减少因盲目性诊刮对老年妇女的伤害.方法 对92例绝经子宫内膜增厚(≥5mm)妇女,分无症状与有症状两组进行临床与病理分析、比较.结果 无症状组63例,正常绝经后内膜47例(75%),良性病变16例(25%),无恶性病变;有症状组29例,正常绝经后内膜15例(52%),良性病变10例(34%),恶性病变4例(14%);22例激素替代治疗者中,有1例是内膜癌,并伴有阴道出血、流液症状.结论 绝经后不伴出血等症状,内膜≥5mm,可免诊刮.激素替代治疗者,在停药、数次出血后,内膜<5mm,同样可以免刮,但两者必须严密监测.     

40岁以下妇女子宫内膜癌刮宫活检的病理诊断问题

目的 探讨40岁以下妇女子宫内膜癌刮宫活检的病理诊断。方法对20例40岁以下子宫内膜癌患者的临床病理资料进行回顾性分析。结果子宫内膜样腺癌18例,腺鳞癌(腺癌伴鳞状上皮分化)1例,浆液性乳头状癌并透明细胞癌1例。子宫内膜样腺癌的组织学特点是子宫内膜腺体失去极性,细胞核变大、变圆、核仁突出,染色质粗或呈空泡状,同时子宫内膜间质消失,代之为肉芽组织或纤维组织,常有炎性反应。子宫内膜样腺癌多数仅累及浅肌层,皆无转移。1例子宫内膜腺鳞癌呈双侧卵巢转移;1例浆液性乳头状癌有盆腔淋巴结转移。结论40岁以下妇女的子宫内膜癌多数为高分化子宫内膜样腺癌,应注意与子宫内膜不典型增生及不典型息肉状腺肌瘤鉴别。     

子宫内膜癌临床病理学研究

目的了解子宫内膜癌的主要临床病理特点、肿瘤的浸润和扩散,以期对临床手术方式选择有所裨益.方法对126例子宫内膜癌患者,重新光镜观察宫内膜癌病理、浸润及扩散情况并进行病理分类、病理分级和临床分期.结果本组中有异常子宫出血124例(98.4%),子宫内膜样腺癌最多(86.5%),临床Ⅰ期占82.1%,G3淋巴结转移率(43.7%)明显高于G2(12.2%)和G1(2.7%),深肌层浸润的淋巴结转移率(43.7%)明显高于浅肌层浸润者(3.2%).结论子宫内膜癌最突出的症状是子宫出血,几乎绝大多数是腺癌.手术时要根据大体观察、术前诊断、术中冰冻等结果,对其组织亚型、病理分级、临床分期、肌层浸润程度等进行综合分析,以选择合适的手术方式.     

绝经期子宫内膜异位症23例临床分析

目的探讨绝经期子宫内膜异位症的临床特点及诊断治疗。方法回顾性分析我院1995．3—2009.3,手术证实的23例绝经后子宫内膜异位的患者的临床资料。结果绝经期子宫内膜异位症术前多无明显症状。主要症状有盆腔包块12例,绝经后阴道流血8例,阴道分泌物增多4例,慢性盆腔疼痛3例。17例（73％）术前误诊,23例均行全子宫＋双附件切除术,术后病理证实合并子宫肌瘤15例,子宫腺肌症6例,子宫内膜癌1例。结论绝经后子宫内膜异位症是一不容忽视的疾病,发病率有增加趋势,由于临床表现不典型,常有漏诊、误诊。全子宫＋双附件切除术是治疗的主要方法。     

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Ⅱ型的前期病变和发生机制

目前,子宫内膜癌的概念成功地整合了传统的组织病理与病理遗传机制两方面的研究进展。根据组织形态学、临床表现和流行病学,将子宫内膜癌分为Ⅰ型和Ⅱ型[1]。Ⅰ型以子宫内膜样癌为代表,占70%~80%;Ⅱ型以浆液性、透明细胞癌为代表,约占15%。Ⅰ型子宫内膜癌的发生与雌激素刺激有关,进展慢,常伴发子宫内膜增生症或子宫内膜上皮内瘤变(endometrial intraepithelial neoplasia,EIN);相反,Ⅱ型子宫内膜癌缺乏与雌激素的关系,临床进展快,最近有关于其前期病变的报道[2~4]。两者的临床病理特征见表1。表1子宫内膜癌病理亚型的临床病理表现Ⅰ型Ⅱ型…     

子宫内膜癌肌层浸润深度的阴道超声诊断

目的探讨阴道超声对子宫内膜癌的术前分期与病理诊断对照的准确性.方法术前应用经阴道超声(TVS)对54例子宫内膜癌患者进行了检查、测量子宫肌层浸润深度,并与术后组织病理学结果对照分析.结果42例可见内膜回声,其平均厚度为14.5±5.4mm(4.8～25mm).TVS准确判断出85.2%患者的肌层浸润深度,44例患者(81.5%)的超声分期准确.多普勒显示深肌层浸润者的阻力指数和搏动指数明显低于无肌层浸润者.结论认为TVS对子宫内膜癌的术前分期和制定个体化治疗方案具有重要作用.     

子宫内膜癌肌层浸润深度的阴道超声诊断

目的探讨阴道超声对子宫内膜癌的术前分期与病理诊断对照的准确性.方法术前应用经阴道超声(TVS)对54例子宫内膜癌患者进行了检查、测量子宫肌层浸润深度,并与术后组织病理学结果对照分析.结果 42例可见内膜回声,其平均厚度为14.5±5.4mm(4.8～25mm).TVS准确判断出85.2%患者的肌层浸润深度,44例患者(81.5%)的超声分期准确.多普勒显示深肌层浸润者的阻力指数和搏动指数明显低于无肌层浸润者.结论认为TVS对子宫内膜癌的术前分期和制定个体化治疗方案具有重要作用.     

Prediction of lymphovascular space invasion in patients with endometrial cancer

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC).Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients'' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis.Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the “LVSI index” as “TD×%MMI×tumor grade×cervical stromal involvement.” The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200.Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.     

PTEN immunohistochemistry in endometrial hyperplasia: which are the optimal criteria for the diagnosis of precancer?

Guidelines recommend protein phosphatase and tensin homolog (PTEN) immunohistochemistry for differentiating between benign endometrial hyperplasia (BEH) and atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN). However, it is unclear when PTEN expression should be defined as ‘lost’ and thus suggestive of AEH/EIN. We aimed to determine the optimal immunohistochemical criteria to define PTEN loss in endometrial hyperplasia, through a systematic review and meta‐analysis of diagnostic accuracy. Electronic databases were searched for studies assessing immunohistochemical expression of PTEN in both BEH and AEH/EIN specimens. PTEN status (‘loss’ or ‘presence’) was the index test; histological diagnosis (‘AEH/EIN’ or ‘BEH’) was the reference standard. Accuracy was quantified based on the area under the curve (AUC) on summary receiver operating characteristic (SROC) curves, for several different thresholds of PTEN expression. Eighteen studies with 1362 hyperplasias were included. Six different criteria to define PTEN loss were assessed. Low diagnostic accuracy was found for complete loss of expression (AUC = 0.71), presence of any null gland (AUC = 0.63), positive cells <10% (AUC = 0.64), positive cells <50% (AUC = 0.71) and moderate‐to‐null intensity (AUC = 0.64). Barely moderate diagnostic accuracy was only found for the subjective criterion ‘weak‐to‐null intensity’ (AUC = 0.78). Therefore, the clinical usefulness of PTEN immunohistochemistry in this field should be further investigated.     

Expression and Clinical Significance of Ghrelin in Endometrial Hyperplasia and Carcinoma of Egyptian Patients

Endometrial carcinoma ranks the seventh most common malignant tumor worldwide. The distinction between atypical endometrial hyperplasia (AEH) and endometrial carcinoma, especially the well-differentiated grade, is particularly difficult with overlapping distinguishing criteria and small biopsy. Ghrelin is 28 amino acid peptide that is synthesized by gastric mucosa and is expressed in a variety of normal and tumor tissues. In endometrial tissue, it is expressed during the menstrual cycle, involved in the uterine development and cyclic growth. Data regarding role of Ghrelin in endometrial carcinoma are contradictory. In the present study, immunohistochemical expression of Ghrelin was evaluated in 55 endometrioid carcinoma cases, as well as 26 endometrial hyperplasia cases. The relationship between Ghrelin expression and clinicopathologic features of endometrioid carcinoma was studied as well. Ghrelin loss or reduced expression was significantly related to endometrioid carcinoma, especially the well-differentiated type, compared with AEH and EIN (p?=?0.000 and 0.006, respectively). Ghrelin loss was also related to poorly differentiated histologic grades of endometrioid carcinoma (p?=?0.04). Ghrelin loss is helpful in differentiation between AEH and EIN from endometrioid adenocarcinoma, especially the well-differentiated grade. It could be also related to poor differentiation.     

转移抑制基因KAI1表达与子宫内膜腺癌进展的关系

目的探讨KAI1蛋白表达与子宫内膜腺癌进展的关系。方法应用免疫组化SP法检测20例正常子宫内膜组织、17例子宫内膜不典型增生和48例子宫内膜腺癌组织中KAI1蛋白的表达情况。结果子宫内膜腺癌中KAI1蛋白的阳性率明显低于正常内膜组织(P<0.01)和内膜不典型增生组织(P<0.01)。KAI1蛋白的表达随子宫内膜腺癌恶性程度(P<0.01),肌层浸润深度(P<0.01)及手术-病理分期(P<0.05)的增高而降低,并与子宫内膜腺癌组织学类型有关(P<0.01),有淋巴结转移的组织中KAI1蛋白阳性率明显低于无转移组织(P<0.01)。KAI1阴性的患者总的生存率低于阳性者(P<0.01,<0.01)。结论KAI1蛋白在子宫内膜腺癌的恶性进展中表达下调,有望成为内膜癌恶性程度评估,转移预测和判断预后的有效指标。     

Malignant transformation of atypical endometrial hyperplasia after progesterone therapy showing germ-cell tumor-like differentiation

A 31-year-old woman was treated for atypical endometrial hyperplasia (AEH) with high-dose medroxyprogesterone acetate (MPA) therapy to preserve fertility. The AEH was found by repeated cytologic and histologic examinations to have completely disappeared with the therapy, but 3 years after her last follow up she required emergency surgery to treat severe genital bleeding. The hysterectomied uterus consisted mostly of poorly differentiated adenocarcinoma, G3 endometrioid type. Minor AEH was present in the exophytic area, in which some glands were cystically dilated. Part of the AEH had transformed into other histologic features with germ-cell-like differentiation, demonstrated by immunohistochemical positive reaction of placental alkaline phosphatase, alpha-fetoprotein, and human chorionic gonadotrophin. Recurrent AEH had undergone malignant transformation, resulting in the development of well- and poorly differentiated adenocarcinoma and tumor exhibiting germ-cell-like differentiation. The patient died of a massive tumor extension 7 months after surgery. The AEH before MPA therapy and the recurrent tumors had genetically different characteristics based on evidence of a loss of heterozygosity, detected at D8S1132 (chromosomal locus, 8q22.1) in the latter but not in the former, by analysis of genetic alterations using microsatellite markers.     

Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas

Mutation of the ARID1A gene and loss of the corresponding protein BAF250a has recently been described as a frequent event in clear cell and endometrioid carcinomas of the ovary. To determine whether BAF250a loss is common in other malignancies, immunohistochemistry (IHC) for BAF250a was performed on tissue microarrays (TMAs) in more than 3000 cancers, including carcinomas of breast, lung, thyroid, endometrium, kidney, stomach, oral cavity, cervix, pancreas, colon and rectum, as well as endometrial stromal sarcomas, gastrointestinal stromal tumours, sex cord-stromal tumours and four major types of lymphoma (diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, mantle cell lymphoma and follicular lymphoma). We found that BAF250a loss is frequent in endometrial carcinomas but infrequent in other types of malignancies, with loss observed in 29% (29/101) of grade 1 or 2 and 39% (44/113) of grade 3 endometrioid carcinomas of the endometrium, 18% (17/95) of uterine serous carcinomas and 26% (6/23) of uterine clear cell carcinomas. Since endometrial cancers showed BAF250a loss, we stained whole tissue sections for BAF250a expression in nine cases of atypical hyperplasia and 10 cases of atypical endometriosis. Of the nine cases of complex atypical endometrial hyperplasia, all showed BAF250a expression; however, of 10 cases of atypical endometriosis (the putative precursor lesion for ovarian clear cell and endometrioid carcinoma), one case showed loss of staining for BAF250a in the atypical areas, with retention of staining in areas of non-atypical endometriosis. This was the sole case that recurred as an endometrioid carcinoma, indicating that BAF250a loss may be an early event in carcinogenesis. Since BAF250a loss is seen in endometrial carcinomas at a rate similar to that seen in ovarian carcinomas of clear cell and endometrioid type, and is uncommon in other malignancies, we conclude that loss of BAF250a is a particular feature of carcinomas arising from endometrial glandular epithelium.     

Adenomyosis involved by endometrial adenocarcinoma is a significant risk factor for deep myometrial invasion

Adenomyosis is commonly seen in association with endometrial adenocarcinoma where it may or may not be involved by malignancy. This study of grade 1 endometrioid adenocarcinoma investigates whether patients with cancer-positive adenomyosis are at a different risk for deep myometrial invasion compared with those with cancer-negative adenomyosis. Ninety-three hysterectomy specimens with FIGO (International Federation of Gynecologists and Obstetricians) grade 1 endometrial endometrioid adenocarcinoma associated with adenomyosis were studied. Four experienced gynecologic pathologists retrospectively reviewed all hematoxylin and eosin-stained sections. Myometrial invasion was confirmed by CD10-negative staining around glands with jagged outline surrounded by inflamed desmoplastic stroma. Adenomyosis was involved by adenocarcinoma in 46 cases, whereas it was carcinoma-negative in 47 cases. Myometrial invasion was found in significantly more carcinoma-positive adenomyosis cases (n = 42, 91.3%) than with carcinoma-negative adenomyosis cases (n = 30, 63.8%) (chi(2) = 12.10; P = .0005). Moreover, myometrial invasion in the outer half was also seen in significantly more carcinoma-positive adenomyosis cases (n = 16, 34.8%) than with carcinoma-negative adenomyosis cases (n = 3, 6.4%) (chi(2) = 11.53; P = .0007). Among all cases of FIGO grade 1 endometrial endometrioid adenocarcinoma associated with adenomyosis, the ones that extend in the adenomyosis gain more invasive advantage, probably through increasing the surface area of its interface with the adjacent myometrium. When compared with tumors that do not involve adenomyosis, these tumors are not only more likely to invade the myometrium but are significantly more prone to achieve deep invasion into the outer half.     

子宫内膜癌淋巴结转移的危险因素及预后分析

目的探讨子宫内膜癌腹膜后淋巴结转移的高危因素及淋巴结转移对于预后的影响。方法回顾性分析2005年1月至2010年12月期间在北京协和医院妇产科进行诊治的289例行腹膜后淋巴结切除的子宫内膜癌患者的临床病理资料,对影响子宫内膜癌腹膜后淋巴结转移的高危因素和影响子宫内膜癌患者预后的因素进行统计分析。结果 1)289例患者中位发病年龄55岁,Ⅰ期224例(77.5%),Ⅱ期13例(4.5%),Ⅲ期45例(15.6%),Ⅳ期7例(2.4%)。289例行盆腔淋巴结切除,30例(10.4%)有盆腔淋巴结转移;96例行腹主动脉旁淋巴结切除,11例(11.5%)有腹主动脉旁淋巴结转移。复发21例(7.3%),死亡11例(3.8%),中位随访时间37个月,中位无瘤生存时间34个月。2)单因素分析显示术前CA125≥35 U/m L、非子宫内膜样癌、组织学分级为G3、深肌层浸润、肿瘤≥2 cm、宫颈间质受累、腹腔冲洗液细胞学阳性及阴道或宫旁受累是淋巴结转移率的高危因素(P0.05)。多因素分析显示术前CA125值≥35 U/m L、低分化、肌层浸润深度≥1/2是淋巴结转移的独立危险因素(P0.05)。3)Kaplan-Meier单因素分析显示,腹腔冲洗液细胞学阳性、阴道或宫旁受累、附件受累及淋巴结转移缩短无瘤生存时间(P0.05);非子宫内膜样癌、低分化、肌层浸润深度≥1/2、腹腔冲洗液细胞学阳性、附件受累及淋巴结转移缩短总生存时间(P0.05)。COX回归多因素分析显示,腹膜后淋巴结转移是5年无瘤生存率的独立预后因素(未转移者92.1%vs转移者65.3%,P=0.002,95%CI 0.078~0.552);虽不是5年总生存率的独立预后因素,但无淋巴结转移者的5年总生存率有高于淋巴结转移者的趋势(未转移者96.1%vs转移者70.0%,P=0.086,95%CI 0.039~1.238)。结论本研究发现:1)肿瘤分化程度和肌层浸润深度对淋巴结转移有预测意义,能够指导子宫内膜癌患者是否进行淋巴结切除术,为个体化治疗奠定理论基础。2)淋巴结转移患者仍然有较无淋巴结转移者预后更差的趋势,因此对于淋巴结转移的患者需要进行辅助治疗,减少复发风险。