宫颈癌组织中Fas、FasL及caspase-8表达及其临床意义

目的 研究Fas、FasL及caspase-8蛋白在宫颈癌组织中的表达及其临床意义，并探讨其在宫颈肿瘤细胞免疫逃避中的作用。方法 采用免疫组化法检测52例宫颈癌、18例宫颈上皮内瘤祥病变组织(CIN)及其肿瘤浸润淋巴细胞(TIL)，10例慢性宫颈炎，10例正常宫颈上皮中Fas、FasL和caspase-8蛋白表达情况。结果 Fas及FasL在宫颈癌组织中的表达率与慢性宫颈炎及正常组织比较有显著性差异(P＜0．05，P＜0．01)，宫颈鳞癌明显高于宫颈腺癌(P＜0．05，P＜0．01)。Fas阳性表达率随着组织学分级的升高而降低，FasL则增高(P＜0．01)；有淋巴结转移者FasL阳性表达率高于无淋巴结转移者(P＜0．01)；Fas及FasL表达与患者年龄、临床分期无关(P＞0．05)。宫颈癌TIL的Fas及FasL表达明显高于CIN(P＜0．01)；caspase-8在宫颈癌组织中的表达明显低于正常宫颈上皮及慢性宫颈炎组织(P＜0．01)，caspase-8表达与宫颈癌患者年龄，临床分期，组织学类型无关(P＞0．05)，有淋巴结转移者明显低于无淋巴结转移者(P＜0．05)，随着组织学分级的降低，caspase-8表达亦明显降低，但无显著性差异。结论 宫颈癌能通过Fas，caspase-8低表达及FasL高表达，逃避机体免疫监视以促使肿瘤发生发展及转移。     

B7-H4及Fas、FasL与宫颈癌免疫逃逸机制的关系

目的:检测免疫共刺激分子B7-H4及Fas、FasL在不同宫颈组织中的表达,研究三者的异常表达与宫颈癌免疫逃逸机制的关系。方法:选择陕西省肿瘤医院病理科2014-2018年的石蜡包埋标本162例,采用免疫组织化学方法检测20例正常宫颈、30例宫颈上皮内瘤变(CIN)和112例I期-IV期宫颈癌组织中B7-H4及Fas、FasL的表达水平。结果:B7-H4在正常宫颈组、CIN组、宫颈癌组的阳性表达率分别为0、20.0%、47.32%,两两相比,具有显著性差异（P<0.05）。在112例宫颈癌病例中FIGO临床分期I期至IV期各期别宫颈癌组织B7-H4的阳表达率分别为16.67%、43.18%、70.83%、85.71%,各组间相比差异具有统计学意义。正常对照组Fas的阳性表达率是85.00％,CIN组43.33％,宫颈癌组41.96％,正常组与CIN、正常组与宫颈癌组相比差异均具有统计学意义（P<0.05）,CIN组与宫颈癌组相比,无明显差异（P>0.05）。FasL的阳性表达率在正常组为20.00%,CIN组为50.00%,宫颈癌组为56.25%,正常组与CIN、宫颈癌组比较,差异具有统计学意义(P<0.05),CIN组与宫颈癌组比较无显著差异;B7-H4阳性宫颈癌组Fas阳性表达率28.30%明显较B7-H4阴性宫颈癌组Fas阳性表达率54.24%低,差异具有统计学意义（P<0.05）;而B7-H4阳性宫颈癌组FasL阳性表达率79.25%明显高于B7-H4阴性宫颈癌组FasL阳性表达率35.59%,差异具有统计学意义（P<0.05）。结论:负性免疫共刺激分子B7-H4和Fas、FasL凋亡蛋白在宫颈癌的发生、进展中起到了重要作用,其协同作用可能为宫颈癌细胞逃逸机体免疫的机制之一。     

Fas和FasL及Caspase-8在宫颈癌组织中的表达及其临床意义

目的 :研究Fas、FasL及Caspase 8在宫颈癌组织中的表达及其临床意义 ,探讨Fas系统在宫颈肿瘤细胞免疫逃避中的作用。方法 :采用免疫组化S P法检测 5 2例宫颈癌、18例宫颈上皮内瘤样病变、10例慢性宫颈炎及 10例正常宫颈上皮Fas、FasL和Caspase 8蛋白表达情况。结果 :Fas及FasL在宫颈癌中的表达与在慢性宫颈炎及正常组织中表达差异有显著意义 ;Fas阳性表达率随着组织学分级的升高而降低 ,FasL则增高 ,P <0 0 1;Fas及FasL与患者的年龄和临床分期无关 ,P >0 0 5。Caspase 8在宫颈癌中的表达明显低于正常宫颈上皮及慢性宫颈炎 ,P <0 0 1;Caspase 8表达与宫颈癌患者的年龄、临床分期及组织学类别无关。结论 :宫颈癌能通过Fas、Caspase 8低表达及FasL高表达逃避机体免疫监视以促使肿瘤发生发展及转移     

宫颈癌组织中LRP16和CIAP2的表达及其意义

目的:探讨宫颈癌组织中LRP16和CIAP2蛋白的表达及其与临床病理特征的关系。方法:采用免疫组化的方法检测正常宫颈组织24例,宫颈上皮内瘤变（CIN）30例（CINⅠ+CINⅡ18例,CINⅢ12例）,宫颈癌组织66例中LRP16和CIAP2的表达,分析其与患者年龄、宫颈癌临床分期、组织学分级、病理类型及有无淋巴结转移的关系。结果:LRP16在正常宫颈组织,CINⅠ+CINⅡ、CINⅢ,宫颈癌组织中的阳性表达率分别为16.67%,33.33%,66.67%,69.70%;CIAP2为8.33%,22.22%,50.00%,53.03%。宫颈癌组和正常宫颈组、CINⅠ-Ⅱ组相比较差异均有统计学意义（P<0.05）,宫颈癌组和CINⅢ组比较差异无明显的统计学意义（P>0.05）。LRP16蛋白的表达水平与CIN及宫颈癌呈正相关,检测LRP16对了解CIN及宫颈癌生物学行为和评估预后具有一定的价值。LRP16和CIAP2的阳性表达率与临床分期、组织学分级和有无淋巴结转移均有相关性（P<0.05）;LRP16和CIAP2的表达存在正相关性（P<0.05）。结论:LRP16和CIAP2在宫颈癌组织中表达水平的上调可能在宫颈癌的发生发展和转移浸润中起着重要的作用。     

Runx3蛋白在宫颈癌组织中的表达及其意义

目的:检测Runx3蛋白在宫颈正常组织、宫颈上皮内瘤变(CIN)和宫颈癌中的表达情况,探讨其与宫颈癌发生发展的关系.方法: 应用免疫组织化学方法(SP法)检测正常宫颈组织、宫颈上皮内瘤变(CIN)及宫颈癌组织中Runx3蛋白的表达情况.结果:Runx3蛋白在宫颈癌组织中的表达明显减少,在正常宫颈、CIN、宫颈癌组织中阳性表达率分别为95.0%、66.7%和26.9%,各组间差异有统计学意义(P<0.05);Runx3蛋白的表达与宫颈癌分化程度、临床分期以及是否淋巴结转移明显相关(P<0.05),而与组织学分型无关(P>0.05).结论:Runx3蛋白的表达异常与宫颈癌的发生、发展密切相关.     

Maspin和Fas在50例宫颈癌中的表达及意义

[目的]分析Maspin和Fas在宫颈癌中的表达及其与临床病理特征间的关系。[方法]应用免疫组化法检测20例正常宫颈、20例宫颈上皮内瘤样变（CIN）、50例宫颈癌组织中Maspin和Fas的表达水平。[结果]正常宫颈、CIN、宫颈癌组织中Maspin阳性表达率分别为85.0%（17/20）,65.0%（13/20）和36.0%（18/50）,三组间有显著性差异（χ2=15.1875,P〈0.05）;Fas的阳性表达率分别为90.0%（18/20）,50.0%（10/20）和38.0%（19/50）,三组间有显著性差异（χ2=15.5329,P〈0.05）。Maspin表达与宫颈癌组织学分化程度、FIGO分期、淋巴结转移有关（P〈0.05）,Fas表达与宫颈癌FIGO分期、淋巴结转移有关（P〈0.05）。[结论]Maspin和Fas在宫颈癌中低表达,两者参与了宫颈癌的发生和发展。     

COX-2和Fas在宫颈癌中的表达及其临床意义

目的:研究COX-2和Fas在宫颈癌中的表达及其与临床病理特征间的关系.方法:采用免疫组化S-P方法检测61例宫颈组织(正常宫颈组织10例,宫颈上皮内瘤样变10例,宫颈癌41例)中COX-2和Fas的表达情况.结果:COX-2和Fas在宫颈癌和正常宫颈组织中及CIN中的表达有显著性差异(P<0.05).COX-2阳性表达和宫颈癌病理分级、淋巴结转移显著相关(P<0.05);Fas阳性表达和淋巴结转移显著相关(P<0.05).宫颈癌组织中COX-2和Fas的表达呈负相关.结论:COX-2和Fas均参与宫颈癌的发生、发展,在宫颈癌中COX-2的高表达和Fas的低表达均提示有淋巴结转移,可作为判断宫颈癌侵袭性的生物学指标.     

宫颈癌组织中sFRP1和β-catenin的表达及其意义

背景与目的:近年来发现Wnt通路中分泌型卷曲相关蛋白1(secreted frizzled related protein 1,sFRPI)、β-连环蛋白(β-catenin)的异常表达与肿瘤的形成密切相关.本研究旨在探讨sFRP1及β-catenin在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和宫颈癌组织的表达及其与宫颈癌形成和预后之间的关系.方法:采用免疫组织化学SP法检测20例正常宫颈组织、30例CIN和78例宫颈癌中sFRPI及R -catenin的表达:分析其表达与宫颈癌临床病理因素的关系及对预后的影响.结果:sFRPI在正常宫颈、CIN及宫颈癌组织中的阳性表达率分别为100.0%、70.0%及33.3%,差异有统计学意义(P<0.05).sFRPI的表达与宫颈癌的临床分期及淋巴结转移显著相关,sFRPI阳性表达者5年生存率高于阴性表达者(79.8%vs 60.5%),差异有统计学意义(P<0.05) ; β-catenin在正常宫颈、CIN及宫颈癌组织中的异常表达率分别为5.0%,43.3%及70.5%,差异有统计学意义(P<0.05).β-catenin的异常表达与宫颈癌的临床分期、淋巴结转移及病理学分级显著相关,正常表达的患者5年生存率高于异常表达者(83.7% vs 59.2%),差异有统计学意义(P<0.05);宫颈癌组织中sFRP1阳性表达与β-catenin的异常表达呈负相关(r=-0.557,P相似文献   

宫颈癌组织中CIP2A和HPV16-E7的表达及其临床意义分析

目的 探讨宫颈癌(Cervical cancer)、宫颈上皮内瘤变(Cervical intraepithelial,CIN)及正常宫颈组织中CIP2A、HPV16-E7的表达及其之间的相互关系。方法 应用免疫组化S-P法检测50例宫颈鳞状细胞癌、34例CINⅠ、40例CINⅡ、45例CINⅢ和12例正常宫颈组织中CIP2A、HPV16-E7蛋白的表达。结果 CIP2A在宫颈癌、CINⅢ阳性表达率分别为68%(34/50)、13.3%(6/45);而在CINⅡ、CINⅠ及正常宫颈组织中阳性表达率均为0%。CIP2A蛋白在宫颈癌中的表达明显高于宫颈上皮内瘤变及正常宫颈组织,且与组织学分级、临床分期及淋巴结转移有关,差异均有统计学意义(P＜0.05)。HPV16-E7蛋白在宫颈癌、CINⅢ、CINⅡ及CINⅠ组织中的阳性表达率分别为72%(36/50)、68.89%(31/45)、67.50%(27/40)及64.71%(22/34);而在正常宫颈组织中阳性表达率为16.67%(2/12)。HPV16-E7蛋白在宫颈癌及宫颈上皮内瘤变组织中的表达明显高于正常宫颈组织,差异均有统计学意义(P＜0.05),且与年龄有关,而与组织学分级、临床分期及淋巴结转移无关。CIP2A 与HPV16-E7蛋白的表达呈正相关(r=0.514,P＜0.05)。结论 CIP2A、HPV16-E7在宫颈鳞状细胞癌中的过表达,提示宫颈癌中CIP2A与HPV16可能相互协调,共同促进宫颈癌的发生发展。     

Survivin与MIF在宫颈癌组织中的表达及意义

目的 探讨Survivin和MIF在宫颈癌组织巾的表达及意义.方法 采用免疫组化方法检测50例官颈癌组织,20例官颈上皮内瘤变(CIN)及lO例正常官颈组织中Survivin和MIF的表达情况.结果 Survivin在宫颈浸润癌组的阳性表达率明显高于正常宫颈组和CIN组,差异有统计学意义(P<0.05),但在正常宫颈组和CIN组Survivin的阳性表达差异无统计学意义(P>0.05).MIF在正常宫颈组织中不表达,在CIN组和官颈癌组表达率增高,且正常宫颈组和CIN组及宫颈癌组中M1F的阳性表达差异有统计学意义(P0.05).Survivin在官颈癌组织中的阳性表达与肿瘤的组织学类型有关(P<0.05),与患者的年龄、肿瘤的临床分期、分化程度、有无盆腔淋巴结转移等无关(P>0.05).MIF在官颈癌组织中的阳性表达与肿瘤的临床分期、分化程度、组织学类型、淋巴结转移及患者的年龄均无关(P>0.05).结论 survivin和MIF作为肿瘤相关因子在宫颈癌的发生发展过程中有重要作用,两者的表达与凋亡机制的紊乱及癌基因与抑癌基凶的水平失衡关系密切.     

宫颈及宫颈癌间质成纤维细胞的分离、鉴定与衰老检测研究

背景与目的：宫颈癌作为最常见的妇科恶性肿瘤之一,近年来发病呈年轻化趋势。目前认为人类乳头瘤病毒(human papillomavirus,HPV)的感染,特别是高危型HPV感染是其发生的主要因素。已有研究证实,在肿瘤发生的微环境中,间质成纤维细胞衰老可能促进上皮性肿瘤的发生,但宫颈癌的发生是否也伴有间质成纤维细胞的衰老鲜见报道。本研究拟对正常宫颈和宫颈癌间质成纤维细胞进行特异性研究,以揭示慢性炎症诱导宫颈癌发生的机制,旨在为宫颈癌的诊治提供新的理论依据。方法：分离纯化正常宫颈成纤维细胞(normal fibroblasts,NFs)和宫颈癌相关成纤维细胞(cancer-associated fibroblasts,CAFs),通过ELISA法检测细胞因子白介素-6(interleukin-6,IL-6)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的分泌水平;并用衰老相关β-半乳糖甘酶染色(senescence-associated β-galactosidase,SA-β-gal)、细胞计数和蛋白质印记法(Western blot)分别鉴定细胞衰老、绘制细胞生长曲线和检测NFs与CAFs中p16蛋白表达。结果：CAFs分泌的细胞因子IL-6和VEGF比NFs高2倍以上(P<0.05);CAFs中SA-β-gal的活性比NFs高;而CAFs中p16水平的表达水平比NFs中高。结论：间质成纤维细胞衰老可能与宫颈癌的发生和HPV密切相关,研究细胞因子介导的宫颈癌间质衰老可能有助于宫颈癌的预防、诊断和治疗。     

Expression patterns of seprase,a membrane serine protease,in cervical carcinoma and cervical intraepithelial neoplasm

BACKGROUND: Seprase is a membrane-bound serine proteinase with gelatinase activity, which may be involved in cancer invasion and metastasis. PATIENTS AND METHODS: We examined the seprase expression patterns in invasive or preinvasive squamous epithelial lesions. RESULTS AND CONCLUSION: No seprase immunoreactivity was found in the atypical epithelial cells and subepithelial stromal cells of CIN1 and 2 lesions. No seprase expression could be detected even in CIN3 lesions. However, in contrast to CIN1 and 2, seprase immunoreactivity was occasionally observed in the subepithelial stromal cells that were associated with moderate or severe inflammatory infiltrates. Some microinvasive carcinomas and all invasive carcinomas showed seprase immunoreactivity in the cancer cells with various degrees of seprase-positive stromal cells. Seprase may be an early marker of tumor invasion in squamous lesions of the uterine cervix.     

Analysis of the levels of CA125, carcinoembryonic antigen, and CA19-9 in the cervical mucus for a detection of cervical adenocarcinoma

To verify whether analysis of the levels of CA125, carcinoembryonic antigen (CEA), and CA19-9 in the cervical mucus is effective for a detection of cervical adenocarcinomas or not, simultaneous measurement of these three tumor markers in the cervical mucus samples from women without gynecologic disorders, with leiomyoma, with cervical squamous cell carcinomas, and with cervical adenocarcinomas was performed. Extremely high levels of CA125 with low levels of both CEA and CA19-9 were demonstrated in the cervical mucus samples from women without gynecologic disorders and with leiomyoma. The cervical mucus samples from cervical adenocarcinomas showed low CA125 levels with extremely high CEA and/or CA19-9 levels. Therefore, analysis of the levels of these three tumor markers in the cervical mucus possibly helps in the diagnosis of cervical adenocarcinomas if CEA and/or CA19-9 show extremely high levels. When a ratio of (CEA + CA19-9)/CA125 was calculated, all women without gynecologic disorders and with leiomyoma showed a ratio less than 0.5, whereas ten of 11 cases of cervical adenocarcinomas had a ratio greater than or equal to 0.5. Only one case of microinvasive adenocarcinoma showed a ratio less than 0.5. Accordingly, the ratio greater than or equal to 0.5 strongly suggested an existence of cervical adenocarcinoma, although it included some cases of squamous cell carcinomas (four of 17 cases).     

Epidemiology, prevention and treatment of cervical cancer in the Philippines

Cervical cancer remains to be one of the leading malignancies among Filipino women. High-risk human papillomavirus (HPV) types, such as 16 and 18, are consistently identified in Filipino women with cervical cancer. Factors identified to increase the likelihood of HPV infection and subsequent development of cervical cancer include young age at first intercourse, low socioeconomic status, high parity, smoking, use of oral contraception and risky sexual behaviors. Cancer screening programs presently available in the Philippines include Pap smears, single visit approach utilizing visual inspection with acetic acid followed by cryotherapy, as well as colposcopy. However, the uptake of screening remains low and is further compounded by the lack of basic knowledge women have regarding screening as an opportunity for prevention of cervical cancer. Prophylactic HPV vaccination of both quadrivalent and bivalent vaccines has already been approved in the Philippines and is gaining popularity among the Filipinos. However, there has been no national or government vaccination policy implemented as of yet. The standard of treatment of cervical cancer is radiotherapy concurrent with chemotherapy. Current researches are directed towards improving availability of both preventive and curative measures of cervical cancer management.     

CT、MRI及正电子发射体层成像CT在宫颈癌诊断中的应用

随着其发生率的增加及临床治疗方式的细化,对宫颈癌术前的明确分期及对肿瘤术后复发及转移的评估尤为重要。同一肿瘤应用不同的影像学检查方法可以出现不同的结果,影响临床诊断和治疗。所以影像学检查在肿瘤术前分期及术后复发病例评估中的作用越来越大。     

Season, sun, sex, and cervical cancer.

INTRODUCTION: Sunlight's UV B component, a known cellular immunosupressant, carcinogen, and activator of viral infections, is generally seasonally available. Venereal human papillomavirus (HPV) transmission, at least in part, causes cervical cancer. We have previously inspected the monthly rates of venereal HPV infection and sunlight fluency in Southern Holland over 16 consecutive years. Both peak in August with at least 2-fold seasonality. The amount of available sunlight and the rate of Papanicolaou (Pap) smear screen-detected HPV are positively correlated. We now investigate whether premalignant and malignant cervical epithelial changes are also seasonal and related to seasonal sunlight fluency. METHODS: We have studied >900,000 consecutive, serially independent, interpretable screening Pap smears obtained by a single cervical cancer screening laboratory in Leiden, Holland, during a continuous 16-year span from 1983 through 1998. The average monthly rates of premalignant and malignant epithelial change were inspected and the annual patterns contrasted to the annual pattern of sunlight fluency at this global location and to monthly average HPV infection rate. Because HPV is venereally transmitted, Dutch seasonal sexual behavior was evaluated by assessment of the annual pattern of Dutch conception frequency as a competing cause for cervical cancer seasonality. RESULTS: (a) Twice as many premalignant and malignant epithelial changes were found among Pap smears obtained in the summer months, with an August peak concurrent with histopathologic evidence of HPV infection and sunlight fluency in Southern Holland. (b) Monthly sunlight fluency is correlated positively with both the monthly rates of Pap smear-detected cervical epithelial dysplasia and carcinomatous histopathology, as well as HPV. (c) Conception frequency, in this location, peaks in Spring not summer, and has a 4.8% annual amplitude. CONCLUSIONS: (a) Cervical epithelial HPV infection and HPV-induced cervical epithelial dysplasia and carcinomatous change may each be novel sun exposure risks and thereby behaviorably avoidable. (b) Because screening Pap smears uncover many abnormalities that resolve spontaneously (false positives), these data may argue for screening and follow-up Pap smear examinations in seasons other than summer in the Northern Hemisphere, to diminish the false-positive smear rate. Global data are available to confirm and further test each of these conclusions.     

DCE-MRI of the hypoxic fraction,radioresponsiveness, and metastatic propensity of cervical carcinoma xenografts

Background and purpose

Locoregional treatment failure and poor survival rates are associated with extensive hypoxia in the primary tumor in advanced cervical carcinoma. The potential of gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the hypoxic fraction, radioresponsiveness, and metastatic propensity of cervical carcinomas was investigated in this preclinical study.

Materials and methods

CK-160 and TS-415 cervical carcinoma xenografts were used as tumor models. DCE-MRI was carried out at 1.5 T, and parametric images of K^trans and v_e were produced by pharmacokinetic analysis of the DCE-MRI series. Pimonidazole was used as a hypoxia marker. Tumor radioresponsiveness was determined by irradiating tumors with five fractions of 4 Gy in 48 h and measuring cell survival in vitro. Metastatic propensity was determined by examining host mice for tumor growth in lymph nodes.

Results

Low values of K^trans were associated with extensive hypoxia and radiation resistance in tumors of both lines and with high incidence of metastases in CK-160 tumors. Associations between v_e and hypoxia, radioresponsiveness, or metastatic propensity were not found in any of the tumor lines.

Conclusion

K^trans is a potentially useful biomarker of tumor hypoxia, radiation resistance, and metastatic growth in advanced cervical carcinoma.     

Quality indicators for the management of endometrial,cervical and ovarian cancer

ObjectiveMeasuring quality indicators improves the quality of care. The aim of this review is to identify a set of quality indicators (QIs) that can be used to measure the standard of treatment for patients with endometrial, cervical and ovarian cancer.MethodsA systematic literature search was performed in the Pubmed and Google Scholar database. Articles related to the field of interest, which covered QIs for the management of endometrial, cervical and ovarian cancer, were included if they were written in English and available in full text. Articles related to prevention, screening, diagnosis, quality of life and patient satisfaction were excluded.ResultsA total of 57 suitable articles was found: 13 for endometrial cancer, 17 for cervical cancer and 27 for ovarian cancer. An overview of the selected QIs was made and classified by type of indicator. Relevant QIs related to the structural organisation of health care are: referral to high volume specialists in high volume hospitals, treatment by specialized gynecological oncologists and discussion of treatment plan by a multidisciplinary team according to current guidelines. Important process measures are: a patient report of high quality, an adequate pretreatment staging and an adherence to treatment guidelines. The ultimate goal is to reduce treatment related morbidity and increase the survival rate, which can be measured as outcome indicators.ConclusionThe proposed set of QIs should be validated and can be implemented into quality assurance programmes to improve the quality of care and the outcome of patients with a gynecological cancer.