子宫颈癌及其癌前病变组织端粒酶活性的研究

目的研究宫颈癌及其癌前病变组织中端粒酶激活的意义.方法应用端粒酶重复序列扩增-酶联免疫吸附法(TRAP-ELISA)及电泳-银染法,对36例宫颈浸润癌及16例宫颈上皮内瘤变(CIN)组织进行端粒酶活性测定,以吸光度(A)值判断端粒酶活性.同时测定11例正常宫颈、6例慢性宫颈炎症及8例癌旁组织端粒酶活性作为对照.结果CIN、宫颈癌及对照组端粒酶活性A值分别为0.398±0.293、1.580±0.819和0.050±0.012,3组比较,差异有极显著性(P＜0.01).端粒酶活性高低与肿瘤分化程度呈负相关,与淋巴结转移呈正相关;与组织学类型、分期、体积大小无关.结论端粒酶的激活发生在宫颈癌病变的早期,可能成为宫颈癌及癌前病变早期诊断和鉴别诊断的指标.     

子宫颈上皮内瘤变端粒酶活性的研究

目的探讨端粒酶激活在宫颈癌变过程中的意义及其作为病情监测方法和预测宫颈上皮内瘤变(CIN)结局的可能性.方法采用端粒重复序列扩增-聚合酶链反应(PCR-TRAP)方法检测了64例CIN患者、21例宫颈癌患者、20例慢性宫颈炎患者及15例正常宫颈妇女宫颈脱落细胞、宫颈活组织检查(活检)组织的端粒酶活性.结果正常宫颈、慢性宫颈炎、CINⅠ级(CINⅠ)、CINⅡ级(CINⅡ)、CINⅢ级(CINⅢ)及宫颈癌患者的宫颈脱落细胞端粒酶的阳性表达率分别为20.0%、25.0%、62.5%、60.0%、82.4%及61.9%;对应的活检组织端粒酶的阳性表达率分别为26.7%、30.0%、50.0%、45.0%、96.4%及95.2%;随着宫颈病变的进展,端粒酶阳性表达率呈逐渐增高趋势(X2细胞=16.28、X2组织=36.98,P均＜0.05).CINⅠ、CINⅡ端粒酶阳性表达率比较,差异无显著性(P细胞=0.24、P组织=0.25);CINⅢ端粒酶阳性表达率高于CINⅠ、CINⅡ(P细胞=0.03、P组织=0.000012);CINⅢ与宫颈癌活检组织端粒酶阳性表达率比较,差异无显著性(P=0.05);宫颈脱落细胞与宫颈活检组织的端粒酶检测结果的对应性良好(X2=46.4,P＜0.05).结论端粒酶激活与宫颈癌变的进程有关,宫颈脱落细胞端粒酶活性检测可以作为CIN病情检测、处理及预后估计的辅助指标.     

人端粒酶逆转录酶在子宫颈癌组织中的表达变化及其意义

目的研究端粒酶在宫颈癌及其癌前病变组织中的表达,探讨人端粒酶逆转录酶(hTERT)作为宫颈癌早期诊断标志物的可能性。方法采用RTPCR方法测定端粒酶mRNA在3株宫颈癌细胞、2株正常的人二倍体细胞、38例宫颈癌、16例宫颈上皮内瘤变(CIN)和20例正常宫颈组织中的表达水平;端粒重复序列扩增酶联免疫吸附法测定端粒酶活性;免疫组化链酶菌抗生物素蛋白过氧化物酶(SP)连接法检测3株宫颈癌细胞、2株正常的人二倍体细胞、21例正常宫颈组织、2例CIN和55例宫颈癌切片中hTERT蛋白的表达水平。结果hTERTmRNA在3株宫颈癌细胞中均表达,而在2株正常的人二倍体细胞中无表达,宫颈癌组织中的阳性表达率为81.6%,高于CIN的37.5%和正常宫颈组织的5.0%,差异有统计学意义(P<0.05);hTERTmRNA的阳性表达率与端粒酶活性有相关性(P<0.01);hTERT蛋白在3株宫颈癌细胞中有表达,2株正常的人二倍体细胞中无表达,正常宫颈组织中阳性表达率为4.8%、CIN为28.0%,均低于宫颈癌组织的65.5%,差异有统计学意义(P<0.05)。结论宫颈癌组织和细胞中hTERTmRNA和蛋白阳性表达率均高于正常宫颈组织,其有可能作为宫颈癌早期诊断的标志物。     

hTERT、HPV与宫颈癌的研究进展

端粒酶活性与恶性肿瘤密切相关,调节端粒酶活性的最主要成分是端粒酶逆转录酶(hTERT).宫颈癌中端粒酶活性高表达,而高危型人乳头瘤病毒(HPV)感染是导致宫颈癌的主要原因,HPVE6、E7通过整合到宿主细胞,可调节hTERT的转录,激活端粒酶,研究hTERT、HPV的相关性,有助于宫颈癌发病机理的阐明.     

hTERT、HPV与宫颈癌的研究进展

端粒酶活性与恶性肿瘤密切相关，调节端粒酶活性的最主要成分是端粒酶逆转录酶(hTERT)。宫颈癌中端粒酶活性高表达，而高危型人乳头瘤病毒(HPV)感染是导致宫颈癌的主要原因，HPVE6、E7通过整合到宿主细胞，可调节hTERT的转录，激活端粒酶，研究hTERT、HPV的相关性，有助于宫颈癌发病机理的阐明。     

端粒酶活性与卵巢上皮性肿瘤临床病理因素相关性分析

目的 探讨端粒酶在上皮性卵巢肿瘤发生发展中的作用,评价端粒酶作为卵巢癌诊断及预后指标的价值。方法 采用端粒酶PCR-ELISA法对25例卵巢上皮性肿瘤包括8例良性(5例浆液性、3例粘液性)、3例交界性(浆液性)和14例恶性(8例浆液性,4例粘液性,2例内膜样),6例正常卵巢表面上皮进行端粒酶活性定量检测。结果 2例良性、2例交界性和12例恶性卵巢上皮性肿瘤及1例正常上皮存在端粒酶活性,端粒酶活性的吸光度(A)平均值分别为0.080±0.070、0.408±0.208、1.659±0.930和0.086±0.060,统计学分析表明恶性卵巢肿瘤中端粒酶活性明显高于良性、交界性肿瘤和正常卵巢组织,端粒酶活性和卵巢上皮性肿瘤组织学类型、临床分期无关;而与肿瘤的分化程度呈负相关。结论 研究结果初步证明端粒酶活性增高在卵巢癌的无限增殖中是一重要环节,并提示端粒酶表达有可能成为卵巢癌早期诊断及判断预后的肿瘤标志物。端粒酶PCR-ELISA法具有定性又定量、特异性较高、敏感性强、简易快速、可避免同位素污染等优点。     

宫颈上皮内瘤变和宫颈癌中端粒酶表达与HPV16、18感染的关系

目的探讨宫颈上皮内瘤变(CIN)和宫颈癌中端粒酶的活化与HPV16、18感染的关系.方法采用免疫组化SP法检测52例CIN和69例宫颈癌中端粒酶催化亚单位(hTERT)的表达,以原位杂交法检测HPV16、18的表达,并以18例正常宫颈组织为对照.结果正常宫颈组织中hTERT无表达,HPV16、18阳性率5.6%(1/18);CIN中hTERT阳性率50%(26/52),HPV16、18阳性率51.9%(27/52),CIN组与对照组比,两者差异均有非常显著性(P＜0.01);宫颈癌组hTERT阳性率87.0%(60/69),HPV阳性率84.1%(58/69),宫颈癌组与CIN和对照组比,两者差异均有非常显著性(P＜0.01).hTERT与宫颈癌分期、组织来源、细胞分化及有无淋巴转移等均无关.无论是CIN还是宫颈癌,hTERT阳性者HPV16、18感染率均明显高于hTERT阴性者,相比差异均有非常显著性(P＜0.01).结论端粒酶的活化与宫颈癌的发生有关,不论是CIN还是宫颈癌阶段端粒酶表达率的高低均与HPV感染率高低呈正相关关系,HPV16、18可能是端粒酶活化的始动因素.     

有卵巢癌家族史妇女卵巢表皮细胞端粒不稳定与增生活性下降

端粒不稳定与肿瘤发生有关,永生化细胞中端粒虽然缩短,但由于端粒酶激活使端粒保持稳定。近年来有报道端粒酶中催化功能亚基对端粒酶活性的作用较RNA部分更加重要,端粒酶激活是细胞永生化与肿瘤发生的关键。在正常卵巢上皮细胞中端粒酶阴性,而在卵巢癌细胞及腹水肿瘤细胞中端粒酶呈阳性。本研究以SV-40大T抗原转染有乳腺癌/卵巢癌家族史妇女的卵巢上皮细胞系(FHIOSE)及无此家族史妇女的卵巢上皮细胞系(NFHIOSE),比较两种转染细胞的生长能力、平均端粒长度及端     

hTERC基因表达在宫颈病变中的临床意义

目的探讨应用荧光原位杂交(FISH)技术检测人类染色体端粒酶(hTERC)基因异常扩增在子宫颈病变中的临床意义。方法选择经过液基细胞学(TCT)检查的112例患者为研究对象,根据组织学结果分组,CIN73例、宫颈癌19例、正常20例,用FISH方法检测脱落细胞hTERC基因的表达情况,其中行HPV检查65人,阳性39例,阴性26例。结果在CIN1、CIN2/3和宫颈癌患者宫颈脱落细胞中hTERC基因的表达率分别是16.67%、51.16%和89.47%,CIN1、CIN2/3和宫颈癌与正常组比较,hTERC基因阳性率差异有统计学意义(P0.001),其中,各组间比较差异有统计学意义(P0.05)。在HPV感染的39例患者中,hTERC基因扩增比例58.97%(23/39),而26例HPV阴性的患者中,其扩增比例为23.08%(6/26),两组比较,差异有统计学意义(P0.05)。结论 hTERC基因的阳性率随宫颈病变级别增高而增加,对宫颈早期病变进展有预测意义。hTERC基因的扩增与HPV感染及宫颈病变程度相关,其扩增可能是HPV感染致端粒酶活性增加的早期事件。     

人染色体端粒酶基因的扩增率与宫颈癌前病变和宫颈癌的研究

目的:探讨人染色体端粒酶基因(hTERC)扩增率与宫颈癌前病变及宫颈癌的关系.方法:应用荧光原位杂交技术(FISH)检测宫颈上皮内瘤变(CIN)组108例(CIN Ⅰ 39例、CINⅡ37例、CINⅢ32例),宫颈癌组24例和正常对照组33例,共165例宫颈脱落细胞中hTERC基因的表达情况.结果:CINⅡ、CINⅢ和...     

New techniques in evaluation of the cervix

The process of parturition is poorly understood, but the cervix clearly plays a key role. Because of this, recent research efforts have been directed at objective quantification of cervical remodeling. Investigation has focused on two basic areas: (1) quantification of tissue deformability and (2) presence, orientation, and/or concentration of microstructural components (e.g. collagen). Methods to quantify tissue deformability include strain elastography and shear wave elasticity imaging (SWEI). Methods to describe tissue microstructure include attenuation and backscatter. A single parameter is unlikely to describe the complexities of cervical remodeling, but combining related parameters should improve accuracy of cervical evaluation. This chapter reviews options for cervical tissue characterization.     

宫颈上皮内瘤样病变Ⅲ级治疗与预后分析

目的探讨宫颈上皮内瘤样病变Ⅲ级(CINⅢ)的治疗方法。方法对1972年至1998年在我院治疗的宫颈原位癌48例和宫颈重度不典型增生28例进行回顾性分析。结果原位癌患者中,行次广泛全子宫切除术的29例和全子宫切除术的11例,术后均无复发;6例行宫颈锥形切除术,1例术后14年再次发生原位癌;重度不典型增生的患者,行子宫切除术和锥切术患者均无复发。结论宫颈CINⅢ发病年龄出现年轻化趋势,全子宫切除术与次广泛全子宫切除术预后相近,全子宫切除术可作为原位癌患者的首选治疗方法;单纯宫颈锥切术有术后复发可能,术后应严密随访;重度不典型增生可行宫颈锥切术或LEEP手术,术后应定期随诊。     

Colposcopic accuracy of obstetrics and gynecology residents

OBJECTIVE: The objective of our study was to determine the accuracy of gynecology residents' colposcopic impressions. METHODS: A retrospective review of colposcopic examinations was performed. Colposcopic impressions were compared to cervical biopsy and the results stratified by level of residency training. kappa Statistics were calculated to determine the strength of correlation between impression and biopsy results. RESULTS: Agreement within one-step between cervical histology and the colposcopic impression was found in 351 (77%) of the subjects. Histology impression agreement occurred in 92% of the nurse practitioner procedures, 77% of the second year resident (R2) cases, 75% of R3 colposcopies and 73% of the R4 procedures. The association between cervical biopsy and impression was highly significant (P<0.0001). However, the strength of the correlation was only slight (kappa=0.197). The kappa value was highest for the nurse practitioners (0.376, fair correlation) and lowest for the R3 residents (0.110, slight correlation). The positive predictive value for the association of any colposcopically detected abnormality with any histologic abnormality was 64.1%. The overall PPV was highest for the nurse practitioners (79.3%) and lowest for the R2 residents (58.7%). CONCLUSIONS: While the colposcopic impressions of gynecology residents were accurate, there was little difference in the accuracy of colposcopic assessment based upon the level of resident training.     

Screening history in women with cervical cancer in a Danish population-based screening program

Objective.

The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer.

Methods.

The study describes the results of a quality control audit, performed on all new cervical cancer cases diagnosed in the years 2008-2009 at two major Danish screening-centers. All relevant cytological and histological cervical samples were reviewed.

Results.

202.534 cytological samples were evaluated in the study period, while 112 women were diagnosed with cervical cancer. The histological diagnoses comprised: 62 (55.4%) squamous cell carcinomas, 20 (17.9%) microinvasive squamous cell carcinomas, 25 (22.3%) adenocarcinomas and 5 cancers of different histology. The mean age of study subjects was 46.6 years. 51 (45.5%) women had deficient screening histories, while 45 (40.2%) women had followed the screening recommendations and had normal cervical samples in review. 11 (9.8%) women were diagnosed with false negative cytology, 2 women had false negative histological tests, while pathological review was not feasible for 3 subjects.

Conclusions.

More than 45% of the cervical cancer cases in our study were due to deficient cervical screening, stressing the importance of increasing the screening-uptake and coverage. 40% interval cancers emphasize the relevance of further cervical testing of women with relevant symptoms, despite of prior normal cervical samples. Finally, 9.8% false negative cytological samples are consistent with previous reports, but still a part of the screening program that should be improved.     

Verification of HPV16 as a good prognostic factor for cervical adeno-adenosquamous carcinoma via an international collaborative study

ObjectiveThis study (Asian Gynecologic Oncology Group [AGOG]13-001/Taiwanese Gynecologic Oncology Group [TGOG]1006) was to validate human papillomavirus (HPV)16 as an independent good prognostic factor and investigate the impact of treatment modalities to cervical adenocarcinoma and adenosquamous carcinoma (AD/ASC).Materials and methodsPatients receiving primary treatment at AGOG and TGOG member hospitals for cervical AD/ASC were retrospectively (1993–2014) and prospectively (since 2014) enrolled. DNA extraction from paraffin-embedded tissue (FFPE) specimens was used for HPV genotyping. Those with suspected endometrial origin were excluded for analysis.ResultsA total of 354 patients with valid HPV results were enrolled, 287 (81.1%) of which had HPV-positive tumors. The top-3 types were HPV 18 (50.8%), HPV16 (22.9%) and HPV45 (4.0%). The HPV16-negativity rates varied widely across hospitals. 322 patients were eligible for prognostic analyses. By multivariate analysis, advanced stage (HR5.8, 95% confidence interval [CI] 2.1–15.8; HR5.8, 95% CI 1.6–20.5), lymph node metastasis (HR4.6, 95% CI 2.7–7.9; HR7.3, 95% CI 3.8–14.0), and HPV16-positivity (HR0.3, 95% CI 0.1–0.6; HR0.3, 95% CI 0.1–0.9) were independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Stage I patients with primary surgery had better 5-year PFS (82.8% vs 50.0% p = 0.020) and OS (89.3% vs 57.1%, p = 0.017) than those with non-primary surgery, while the propensity scores distribution were similar among the treatment groups.ConclusionThis study confirmed that HPV16-positivity was a good prognostic factor for PFS and OS in AD/ASC, and patients seemed to have better outcome with primary surgery than non-primary surgery.     

Clinical implications of the interaction between HPV and HIV infections

HIV-related immunodeficiency has complex effects on female genital HPV, which include increased risks of infection, multiple types, persistence, reactivation and the risk to develop pre-invasive and invasive disease.Reconstitution of immunity with anti-viral drugs improves cellular immunity, but the risk of HPV-related malignancy remains higher than background incidences and presents at younger ages. Early initiation of antiretroviral therapy (ART) allows improved retention of immune memory through existing antibodies and T-cell clones and improves long-term outcomes.Suggestions of a higher risk to contract HIV if there is existing genital HPV infection are supported and explained by pathophysiological cervical changes, including inflammation.HIV–HPV interactions should influence public health decisions towards prioritising large-scale prepubertal HPV-vaccine roll-out, secondary cervical cancer prevention and early detection programmes for HIV-infected women and early initiation of ART.This chapter will also focus on special considerations for the management of women with co-infection with these two viruses and genital HPV-related diseases.     

2005年中国12家医院宫颈癌机会性筛查资料分析

目的:探讨中国不同地区进行宫颈癌机会性筛查的价值.方法:收集分析2005年全国12家医院门诊进行宫颈癌机会性筛查(oppommistic screening,OS)的资料,筛查方法包括液基细胞学、巴氏细胞学、高危型HPV检测,以及中国癌症基金会推荐的Ⅰ方案(液基细胞学检查加高危型HPV DNA检测)、Ⅱ方案(巴氏涂片加高危型HPV DNA检测)、Ⅲ方案(醋酸白肉眼检查法);并经阴道镜检查,病理确诊宫颈病变及宫颈癌.结果:共收治门诊患者1242952例次,其中接受OS202231例次,占门诊例次16.27%.筛查方法依次为液基细胞学84082例(41.58%),巴氏细胞学79426例(39.27%),Ⅰ方案23658例(11.70%),Ⅱ方案6504例(3.22%),检测HPV筛查者5976例(2.96%);Ⅲ方案2585例(1.28%).最普遍采用的筛查方法是细胞学检查(液基及巴氏方法)占95.76%.检出宫颈癌前病变(CIN Ⅰ+CIN Ⅱ+CIN Ⅲ)共5146例(2.54%),宫颈癌1134例(0.56%).结论:医院内就诊人群宫颈病变检出率高,应高度重视其机会性筛查,及时进行规范性治疗.     

Intravaginal administration of 9-deoxo-9-methylene-16,16-dimethyl PGE2 for cervical dilation prior to suction curettage

The study objective was to evaluate the safety and efficacy of a single 16, 16-dimethyl prostaglandin E2 (PGE2) vaginal suppository for achieving nonmechanical dilation when administered 12 hours prior to a 1st trimester suction curettage. 20 women between 7 and 12 weeks gestation who wanted an abortion volunteered to be the study subjects. 4 women were primigravidas and 16 were multiparous. All the women had normal medical histories and clinical examinations. Cervical dilatation, if any, was measured with Hegar dilators and recorded in millimeters. The serum concentration of prostaglandin reached its highest levels 4 hours following the insertion of the vaginal suppository. A higher level between 2 and 4 hours cannot be ruled out. Serum progesterone levels showed a slight decrease in 3 patients and no significant change in the other 4 patients. Cramping was noted in 17 of 20 patients. Its onset occurred between 1 hour and 8 hours post insertion. Vaginal bleeding occurred in 19 patients 1-12.5 hours. All patients were found to have a significant degree of cervical softening and cervical dilation when examined at 12 hours following the insertion of the suppository. 16 patients (80%) did not require any further medical dilation. The additional amount of cervical dilation for the 4 remaining patients ranged from 1 mm to 3 mm and was greatly facilitated by a softened cervix. 2 of these 4 women were primigravidas. 10 patients passed "tissue" per vagina during the observation period, prior to the termination procedure. Chorionic villi was confirmed by histologic examination in only 3 instances. The systemic absorption of the paracervical anesthetic was apparently increased since the initial group of patients complained of dizziness, numbness of tongue, and/or bitter taste in mouth. Study results indicate that a single 16, 16-dimethyl PGE2 vaginal suppository can "prime" the cervix so the further mechanical dilation was easily accomplished and in most cases (80%) was completely eliminated.     

Dicer1在宫颈肿瘤组织中的表达及意义

目的:探讨Dicer1在正常宫颈上皮、宫颈上皮内瘤变和宫颈鳞癌的表达及意义。方法:Western blot和RT-PCR法检测正常细胞系(End1/E6E7)、宫颈内瘤变细胞系(S12)及宫颈癌细胞系(Ca Ski、He La、Si Ha和C33A)中Dicer1蛋白及其mRNA表达水平,免疫组织化学技术检测Dicer1在正常宫颈、宫颈上皮内瘤变和宫颈鳞癌中的表达水平。结果:正常宫颈上皮细胞系Dicer1表达水平低于宫颈癌细胞系表达量。随着恶性程度增加,Dicer1呈驼峰状表达,即在正常宫颈组织及Grade III级宫颈鳞癌中表达较低,但在宫颈上皮内瘤变及高分化宫颈肿瘤(grade I级)中表达较高。结论:Dicer1在正常宫颈、宫颈上皮内瘤变和宫颈鳞癌中的表达有差异,为进一步研究Dicer1在宫颈癌发生发展中的作用及分子机制提供依据。