p16基因蛋白在宫颈癌中的表达

目的:观察细胞周期调节蛋白抑制因子p16在宫颈癌组织中的表达,并探讨其与宫颈癌的关系。方法:应用SP免疫组化法检测11例正常宫颈上皮,9例宫颈上皮内瘤样病变(CIN)和48例宫颈癌石蜡包埋组织切片中p16基因蛋白表达情况。统计处理用SSPS10.0软件分析系统。结果:在正常宫颈上皮、CIN和宫颈癌组织中,p16表达的阳性率分别为18.18％、66.67％、87.50％。从正常宫颈到CIN到宫颈癌组织中p16表达呈现逐渐升高的趋势。宫颈癌组织p16表达明显高于正常宫颈组织,具有极显著性差异(P<0.001),CIN和正常宫颈上皮比较,p16表达无显著性差异(P>0.05)。p16表达与宫颈癌的临床分期、组织类型、分化程度以及淋巴结转移均无显著相关性(P>0.05)。结论:细胞周期调节蛋白抑制因子p16基因蛋白高表达参与宫颈癌的癌变过程。     

人乳头状瘤病毒和EB病毒在子宫颈上皮内瘤变中的表达

目的:探讨人乳头状瘤病毒(HPV)和EB病毒(EBV)在子宫颈上皮内瘤变(CIN)中的表达.方法:采用原位杂交对130例CIN(CIN1 50例,CIN2 40例,CIN3 40例)、子宫颈癌10例、子宫颈湿疣样病变10例、子宫颈正常黏膜10例的HPV(高危型16/18、低危型6/11)和EBV进行检测.结果:HPV16/18在CIN1、CIN2、CIN3的阳性表达率分别是44.0%、37.5%和62.5%,子宫颈癌为8/10,子宫颈湿疣样病变为10/10,子宫颈正常黏膜为3/10,差异有统计学意义(P<0.01).HPV6/11在CIN1、CIN 2、CIN3的表达率分别是36.0%、52.5%和70.0%,在子宫颈癌中的表达是6/10,子宫颈湿疣样病变9/10,子宫颈正常黏膜3/10,差异有统计学意义(P<0.01).HPV16/18和HPV6/11在CIN1、CIN2、CIN3中联合表达率分别为26.0%、22.5%和50.0%,子宫颈癌为6/10,子宫颈湿疣样病变为7/10,子宫颈正常黏膜为2/10,差异有统计学意义(P<0.01).EBV在CIN1、CIN2、CIN3的阳性表达率分别是24.0%、12.5%和22.5%,子宫颈癌为3/10,子宫颈湿疣样病变为0/10,子宫颈正常黏膜为0/10,差异无统计学意义(P>0.05).结论:HPV感染是引起CIN的主要致病因子,临床上往往是多种亚型混合感染.EB病毒在CIN和子宫颈癌表达的意义仍有争议.     

Expression of Survivin, CyclinD1, p21^WAF1, Caspase-3 in Cervical Cancer and Its Relation with Prognosis

Summary The implications of Survivin, CyclinD1, p21^WAF1, Caspase-3 in the development, progression and prognosis in cervical cancer were investigated. By using immunohistochemical SP method, the expression of Survivin, CyclinD1, p21^WAF1, Caspase-3 was detected in 41 cases of cervical cancer, 17 cases of cervical intraepithelial neoplasia (CIN) and 10 cases of normal tissues, and their relation with pathological grade, clinical stage, metastasis and survival time was analyzed. The results showed that the positive expression rate of Survivin, CyclinD1 in cervical cancer was significantly higher than in CIN group and normal control group (P<0.05). The median survival time in the patients with cervical cancer positive for Survivin and CyclinD1 was significantly shorter than in those with negative expresion (P<0.05). The expression of both Survivin and CyclinD1 was not related with tumor grade, clinical stage and metastasis (P>0.05). The positive expression rate of p21^WAF1, Caspace-3 in cervical cancer was significantly lower than in CIN group and normal control group (P<0.05), and had a close relation with tumor grade (P<0.05). The expression of Survivin in cervical cancer in cervical cancer was negatively associated with that of Caspase-3 (P<0.01), but positively with that of CyclinD1 (P<0.01). Cox Multivariate analysis revealed that Survivin was the independent prognostic indicator influencing the survival time of the patients with cervical cancer (P<0.05). It was suggested that the high expression of Survivin or CyclinD1, and low expression of p21^WAF1 or Caspace-3 was closely correlated with the development of cervical cancer. Survivin and CyclinD1 could be used as a useful indicator to predict the prognosis of cervical cancer. LU Shi, female, born in 1967, Doctorial Candidate     

Expression of Pinl and Ki67 in Cervical Cancer and Their Significance

In order to investigate the expression levels of Pinl mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pinl gene was examined by RT-PCR, and the expression of both Pinl and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pinl were higher in cervical cancer than in normal cervical tissues （P〈0.05）. The expression of Pinl protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer （P〈0.05）. No significant difference in the Pinl expression was found between disease stages （FIGO）, pathological grades or pelvic lymph node metastasis status （P〉0. 05）. The expression of Pin1 was significantly higher in adenocarcinoma than in squamous carcinoma of the uterine cervix （P〈0.05）. In cervical cancer, the overexpression of Pinl was positively correlated with that of Ki67 （P〈 0. 05）. These results suggested that the overexpression of Pinl was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pinl may serve as a potential marker for cervical cancer diagnosis.     

HPV L1壳蛋白在宫颈脱落细胞中的表达及临床意义

目的 探讨人乳头状瘤病毒(HPV)L1壳蛋白在宫颈不同病变脱落细胞中的表达和临床意义.方法 收集2008年1月至2009年5月到北京大学深圳医院宫颈门诊就诊患者的宫颈脱落细胞标本309例,其中正常或慢性宫颈炎33例、宫颈上皮内瘤变(CIN)I级168例、CIN Ⅱ/Ⅲ级84例和鳞状细胞癌(SCC)24例,用免疫细胞化学法检测HPV L1壳蛋白在宫颈脱落细胞中的表达.结果 在正常宫颈或慢性宫颈炎、CINI、CINⅡ/Ⅲ和SCC中,HPV L1壳蛋白阳性表达率分别为27.3%(9/33)、66.7%(112/168)、25.0%(21/84)、0%(0/24).其中CINI组、SCC组与正常或慢性宫颈炎组比较,CINI组与CINⅡ/HI组比较,CINI、CINⅡ/Ⅲ组与SCC组比较差异均有统计学意义(均P<0.01),随病变程度的加重,HPV L1壳蛋白阳性表达率呈下降的趋势.分别以30岁和40岁为界分组,不同年龄组间HPV L1壳蛋白的表达差异均无统计学意义(均P>0.05).在高危型HPV DNA负荷量≥1 000 RLU/PC组HPV L1壳蛋白表达率为73.1%,与负荷量<1 000 RLU/PC的各组相比,其表达率明显增加(均P<0.05).HPV L1壳蛋白检测CINⅡ/Ⅲ以上病变的敏感度、特异度、阳性预测值和阴性预测值分别为80.6%、60.2%、52.1%和85.2%.结论 HPV L1壳蛋白在CIN和SCC中的阳性表达率随着病变程度加重呈下降趋势,有望成为预测宫颈癌前病变进展的生物学标志物.     

HPV16E6的表达与宫颈鳞癌发病的相关性研究

目的研究人乳头瘤病毒16E6(HPV16E6)蛋白在宫颈鳞癌中的表达及意义。方法应用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连接法观察40例宫颈鳞癌、30例宫颈上皮内瘤样病变(C IN)和30例正常宫颈组织中HPV16 E6的表达。结果 HPV16E6在正常宫颈组织、C IN和宫颈鳞癌组织中的阳性表达率分别为:13.3%、53.3%、82.5%,各组间表达率比较,差异有统计学意义(P<0.01)。HPV16E6蛋白阳性表达在宫颈鳞癌病理分级、临床分期中的比较,差异无统计学意义(P>0.05)。结论 HPV16E6在宫颈鳞癌的发生发展中起重要作用,可能是宫颈鳞癌发病机制之一。对HPV16E6蛋白的致病机制进一步研究,有助于揭示宫颈癌的发病机制,可能用于临床宫颈癌诊断、预防和基因治疗。     

宫颈病变患者人乳头瘤病毒16亚型E2基因多态性检测

目的分析宫颈病变中人乳头瘤病毒（HPV）16亚型E2基因的多态与宫颈病变的关系,了解E2基因变异情况及其与宫颈
病变的相关性。方法应用PCR和高分辨率熔解曲线方法针对379例HPV高危亚型阳性宫颈脱落细胞样本进行HPV16感染
情况及HPV16亚型E2基因68位点和133位点多态分布情况进行检测。结果379例HPV高危亚型阳性宫颈标本共检出78例
HPV16亚型阳性,其在宫颈癌、CINⅡ~Ⅲ、CINⅠ、炎症患者中的检出率分别为44.8%、31.5%、24.1%和9.6%;HPV16E2基因
68C和133G的频率在中重度宫颈内瘤样病变和宫颈癌中明显高于轻度上皮内瘤样病变和炎症患者（P<0.05）。结论HPV16是
导致宫颈恶性病变的重要致病因素;随着病理类型的进展,HPV16感染率也逐渐增加;同时基因位点改变说明HPV16E2基因
单核苷酸变异可能使致癌能力发生改变。
     

宫颈脱落细胞microRNA-508-3p、ROCK1的表达及其对宫颈癌的诊断价值研究

目的 探究宫颈脱落细胞microRNA-508-3p（miR-508-3p）、ROCK1的表达及其对宫颈癌的诊断价值。方法 选取2016年2月—2019年9月诸暨市人民医院收集的宫颈脱落细胞标本172例,其中正常组70例、宫颈上皮内瘤变组54例、宫颈癌组48例。通过qRT-PCR、免疫组织化学、Western blotting检测各组细胞miR-508-3p、ROCK1的表达,荧光素酶报告实验验证宫颈病变脱落细胞miR-508-3p与ROCK1的相关性,观察宫颈癌脱落细胞miR-508-3p、ROCK1表达与宫颈癌患者临床资料的关系,通过受试者工作特征（ROC）曲线评估宫颈病变脱落细胞miR-508-3p、ROCK1表达对宫颈病变的诊断价值。结果 与正常组比较,宫颈癌组和宫颈上皮内瘤变组miR-508-3p降低（P <0.05）,ROCK1 mRNA、ROCK1 mRNA阳性率、ROCK1蛋白相对表达量升高（P <0.05）;与宫颈上皮内瘤变组比较,宫颈癌组miR-508-3p降低,ROCK1 mRNA、ROCK1 mRNA阳性率、ROCK1蛋白相对表达量升高（P <0.05）。宫颈癌组、宫颈上皮内瘤变组miR-508-3p与ROCK1 mRNA呈负相关（r =-0.6678和-0.5234,均P =0.000）,ROCK1是miR-508-3p的直接靶基因。miR-508-3p、ROCK1水平与宫颈癌患者FIGO分期、淋巴结转移有关（P <0.05）,与年龄、绝经情况、肿瘤直径及病理类型无关（P >0.05）。在诊断宫颈癌和宫颈上皮内瘤变时,miR-508-3p的ROC曲线下面积（AUC）分别为0.946（95% CI：0.899,0.993）和0.851（95% CI：0.782,0.921）,敏感性为87.1%（95% CI：0.776,1.654）和84.3%（95% CI：0.746,1.589）,特异性为100.0%（95% CI：1.000,2.000）和79.6%（95% CI：0.702,1.497）;ROCK1的AUC分别为0.949（95% CI：0.892,1.000）和0.905（95% CI：0.852,0.958）,敏感性为89.6%（95% CI：0.810,1.706）和77.8（95% CI：0.667,1.445）,特异性为100.0%（95% CI：1.000,2.000）和88.6%（95% CI：0.812,1.698）。随访1年后,48例宫颈癌患者中生存42例,死亡6例。生存组miR-508-3p高于死亡组（P <0.05）,ROCK1 mRNA相对表达量低于死亡组（P <0.05）。结论 宫颈脱落细胞miR-508-3p、ROCK1在宫颈癌患者中表达异常,其中miR-508-3p下调,ROCK1上调,两者呈靶向负调控关系,并与宫颈癌患者FIGO分期及淋巴结转移密切相关,具有一定的宫颈癌诊断价值,可作为早期宫颈癌筛查的潜在生物学指标。     

Relationship between the Expression of Telomerase and Human Papillomavirus Infection in Invasive Uterine Cervical Carcinoma

Telomerase activity was examined in invasive cervical carcinoma to assess whether it is activated during cervical malignant transformation and to look for its possible association with hu-man papillomavirus(HPV) infection.Histologically confirmed invasive cervical carcinomas and be-nign cervices were assayed for telomerase activity by using a modified telomere repeat amplification protocol(TRAP).The same cases were subjected to polymerase chain reaction(PCR) detection of HPV by using consensus primers and type-specific(HPV types 16 and 18) primers.Telomerase activ-ity was detected in 40 of 45(88.9%) invasive cervical carcinomas and 2(all chronic cervicitis) of 50(4%) benign cervical lesions.HPV was detected in 36(24 HPV-16 and 4 HPV-18 cases) of 45(80%) invasive cervical carcinomas and 20(11 HPV-16 and 1 HPV-18 cases) of 50(40%) benign cervical changes.There was a significant correlation between the expression of telomerase with histological grade(φ=0.44,P<0.005),but no correlation was found between telomerase expression and HPV-18(P>0.05).Although larger sample studies are needed,there seems to be a clear association between telomerase upregulation and HPV status,mainly HPV-16 infection.     

Correlation between physical status of human papilloma virus and cervical carcinogenesis

The prevalence of human papilloma virus (HPV)-16 in patients with cervical cancer,the physical status of HPV-16 in patients with cervical lesions,and the role of HPV-16 integration in cervi-cal carcinogenesis were investigated.HPV genotyping was performed by using PCR approach with the primer GP5+/GP6+ and type-specific primer on biopsy specimens taken operatively from 198 women.Multiple PCR was done to detect physical status of HPV-16 in a series of cervical liquid-based cytology samples and biopsy specimens obtained from different cervical lesions with HPV-16 infection,includ-ing 112 specimens with cervical cancer,151 specimens with CINⅠ,246 specimens with CINⅡ and 120 specimens with CINⅢ.The results showed that there were 112 cervical cancer samples (56.57% of total cervical cancer patients) with HPV-16 infection.The frequency of HPV-16 pure integration was 65.18% (73/112),56.57% (47/120),23.58% (58/246) and 7.95% (12/151) in cervical cancer,CINⅢ,CINⅡand CINⅠ patients respectively.In situ hybridization was performed on some paraffin-embedded sections of CINⅡ,CINⅢ and cervical cancer to verify the physical status of HPV-16 infection.Sig-nificant difference was observed between cervical cancer and CINⅠ,CINⅡ,CINⅢ in the frequency of HPV-16 integration (P<0.01).It is suggested that HPV-16 is the most prevalent type and is associated with cervical cancer.In the case of HPV-16 infection there are close associations between the severity of cervical lesions and the frequency of HPV-16 integration.The application of testing HPV genotyping and physical status based on detection of HC-Ⅱ HPV DNA would be in favor of predicting the progno-sis of cervical precancerosis and enhancing the screening accuracy of cervical cancer.     

Maspin、bFGF在宫颈病变中的表达及与高危型HPV的相关性研究

目的:通过检测乳腺丝氨酸蛋白酶抑制剂(Maspin)、碱性成纤维细胞生长因子(bFGF)在慢性宫颈炎、宫颈上皮内瘤样变(CIN)及宫颈癌组织中的表达,探讨两者的相关性及与高危型人乳头状瘤病毒(高危型HPV)感染之间的关系。方法:宫颈石蜡组织标本166例,其中高危型HPV(+)组106例(慢性宫颈炎20例、CINⅠ级20例、CINⅡ级20例、CINⅢ级20例、宫颈癌组26例);HPV(-)组60例(CINⅠ级35例、CINⅡ级20例、CINⅢ级5例)。应用SP法检测Maspin、bFGF的表达情况。结果:(1)在高危型HPV(+)组中,Maspin蛋白的阳性表达率呈逐渐下降趋势(P<0.05),且在CINⅢ级组中的表达同慢性宫颈炎组、CINⅠ级组、CINⅡ级组相比,差异均有统计学意义(均P<0.05),在宫颈癌组中的阳性表达与CIN各组、慢性宫颈炎组相比较,差异均有统计学意义(均P<0.05);bFGF的阳性表达率呈逐渐增加趋势(P<0.05),bFGF阳性表达率在宫颈癌组表达率最高,显著高于慢性宫颈炎组、CINⅠ级组、CINⅡ级组,差异均有统计学意义(均P<0.05)。在HPV(-)组中,Maspin蛋白的表达依次降低,各组间比较差异均无统计学意义(P>0.05);bFGF的表达依次升高,但差异无统计学意义(P>0.05)。(2)Maspin、bFGF蛋白的表达呈负相关,两者与高危型HPV分别呈负、正相关。结论:高危型HPV可能通过P53调节通路下调Maspin的蛋白表达及上调bFGF的蛋白表达,导致CIN直至宫颈癌的发生。     

宫颈癌前病变和宫颈癌组织中凋亡相关基因survivin的表达及其与人乳头状瘤病毒感染的关系

目的探讨凋亡相关基因survivin在宫颈癌前病变和宫颈癌组织中的表达及其与人乳头状瘤病毒（HPV）感染的相关性.方法选取76例宫颈癌前病变或宫颈癌患者,另取10例正常宫颈组织作为对照.应用免疫组织化学SP法检测各组宫颈组织中凋亡相关基因survivin的表达;设计高危型HPV（HPV16,18,31,33,58等）通用引物,以touch-down PCR法检测各组宫颈组织中高危型HPV的感染率.结果（1）从正常宫颈→癌前病变→宫颈癌,survivin表达逐渐增强（P＜0.05）;（2）survivin表达与宫颈癌组织学分级有关（P＜0.05）,而与年龄、临床分期及组织学分型无关（P＞0.05）;（3）从正常宫颈→癌前病变→宫颈癌,高危型HPV阳性率逐渐升高（P＜0.05）;（4）高危型HPV感染率在不同年龄、临床分期、组织学分级及组织学分型中,均无统计学差异（P＞0.05）;（5）survivin与高危型HPV在宫颈癌组织中的表达呈正相关（P＜0.05）.结论survivin表达及高危型HPV感染可能与宫颈癌的发生、发展密切相关,两者在宫颈癌的发病机制中可能起着协同作用.     

Caveolin-1在子宫颈癌及上皮内瘤中的表达及其与VEGF的关系

研究小凹蛋白-1(Caveolin-1)和血管内皮生长因子(VEGF)在正常宫颈、慢性宫颈炎、宫颈上皮内瘤变(CIN)和浸润性宫颈癌组织中的表达,以及与宫颈癌临床病理特征的关系,同时探讨Caveolin-1和VEGF的相关性。方法以正常子宫颈组织30例为对照,应用免疫组织化学SP法检测慢性宫颈炎40例、CINⅠ-Ⅱ级30例、CINⅢ级20例、浸润性宫颈癌40例(TNM分期Ⅰ期21例和Ⅱ期19例)的Caveolin-1、VEGF的表达水平。结果Caveolin-1蛋白在正常宫颈、慢性宫颈炎、CINⅠ-Ⅱ级、CINⅢ级及浸润性宫颈癌组织中的阳性表达率分别为100.00%(30/30)、95.00%(38/40)、83.33%(25/30)、75.00%(15/20)和72.50%(29/40),呈渐进性降低(P<0.05);而VEGF蛋白在正常宫颈、慢性宫颈炎、CINⅠ-Ⅱ级、CINⅢ级及浸润性宫颈癌组织中的阳性表达率分别为10.00%(3/30)、15.00%(6/40)、26.67%(8/30)、45.00%(9/20)和90.00%(36/40),呈渐进性增高(P<0.05)。Caveolin-1、VEGF蛋白在宫颈癌中的表达与年龄、TNM分期无关(P>0.05),与病理分级、浸润深度、区域淋巴结转移有明显关系(P<0.05);Caveolin-1蛋白的表达与肿瘤大小有关系(P<0.05),而VEGF蛋白的表达与肿瘤大小无关(P>0.05)。浸润性宫颈癌及CINⅢ级中Caveolin-1蛋白与VEGF蛋白的表达呈负相关性(列联系数C分别为0.498、0.538,均P<0.05)。结论 Caveolin-1、VEGF是宫颈癌发生中的早期事件,两者可能通过相反的作用机制参与宫颈癌的发生、发展及血管生成过程。     

人乳头瘤病毒16/18、Bcl-2和Survivin在宫颈癌组织中的表达

目的探讨人乳头瘤病毒(HPV)16/18、Bcl-2、Survivin在宫颈癌组织中的表达及意义。方法收集2010年4月至2012年7月湖北省肿瘤医院保存的宫颈癌组织标本80例、宫颈上皮内瘤样病变(CIN)组织标本70例及正常宫颈组织标本32例,采用原位杂交法检测3种组织中HPV16/18和Survivin的表达,采用免疫组织化学方法检测Bcl-2表达,并分析其表达情况与宫颈癌临床病理特征的关系。结果 Survivin mRNA在宫颈正常组织、CIN及宫颈癌组织中的阳性表达率分别为6.25%、45.71%和77.50%,Bcl-2蛋白在宫颈正常组织、CIN及宫颈癌组织中的阳性表达率分别为3.13%、40.00%和71.25%,HPV16/18 DNA在宫颈正常组织、CIN及宫颈癌组织中的阳性表达率分别为3.13%、51.43%和83.75%,3种组织中Survivin mRNA、Bcl-2蛋白、HPV16/18 DNA阳性表达率比较差异均有统计学意义(P<0.01)。Survivin mRNA、Bcl-2蛋白及HPV16/18 DNA在CIN组织中的表达与CIN分级有相关性,Survivin mRNA、Bcl-2蛋白及HPV16/18 DNA在CINⅢ级中的阳性表达率显著高于CINⅠ、Ⅱ级(P<0.01)。Bcl-2蛋白的表达与宫颈癌组织分化程度及淋巴结转移有相关性(P<0.01),但与宫颈癌组织类型、临床分期及肿瘤生长类型无显著相关性(P>0.05)。Survivin mRNA、HPV16/18 DNA表达与宫颈癌的组织分化程度、临床分期及淋巴结转移有相关性(P<0.01,P<0.05),但与宫颈癌的组织类型及肿瘤生长类型无相关性(P>0.05)。结论 HPV16/18、Bcl-2和Survivin的高表达可能与宫颈癌的发生发展有关,HPV16/18、Bcl-2和Survivin的检测有助于宫颈癌的早期诊断、手术疗效评价及预后判断。     

高危型人乳头状瘤病毒E6/E7 mRNA在宫颈CIN2+病变筛查中的应用价值

目的探讨高危型人乳头状瘤病毒(HR-HPV) E6/E7 mRNA在子宫颈上皮内瘤变中度及以上(CIN2+级)病变筛查中的临床应用价值。方法选取2016年6月至2017年6月在北京市垂杨柳医院因接触性阴道出血或疑似宫颈病变妇科门诊就诊的患者307例,均行液基薄层细胞检查(TCT)、HPV DNA、HPV E6/E7 mRNA的检测,并行阴道镜检查及活检。以病理结果为金标准,将病检结果为高级别鳞状上皮内病变(HSIL,包括CIN2和CIN3)或宫颈鳞癌或宫颈腺癌的71例患者作为观察组,记为CIN2+;将病检结果正常和低级别鳞状上皮内病变(LSIL,包括CIN1)的236例患者作为对照组,记为CIN2-。分析TCT、HPV DNA、HPV E6/E7 mRNA的灵敏度和特异度差异。结果 HPV E6/E7mRNA及HPV DNA对CIN2+诊断的特异度分别为79. 66%及19. 49%,差异有统计学意义(P <0. 05)。HPV E6/E7mRNA联合TCT及HPV DNA联合TCT检测对CIN2+诊断的特异度分别为82. 63%及35. 17%,差异有统计学意义(P <0. 05)。HPV E6/E7 mRNA、HPV DNA在筛查CIN2+的ROC曲线下面积分别为0. 8420和0. 5693,差异有统计学意义(P <0. 05)。结论 HPV E6/E7 mRNA较HPV DNA检测筛查宫颈CIN2+的病变效果更好,HPVE6/E-7mRNA联合TCT检测能够提高对CIN2+的病变筛查的特异性。     

宫颈病变患者SHP-2与CD4+T表达意义的研究

目的了解SHP-2与CD4＋T在患者血液中的表达情况及关系,探讨宫颈癌发生的免疫机制。方法 45例宫颈癌患者,32例CIN患者,14例正常宫颈患者。Westernblot方法检测人外周血淋巴细胞中SHP-2蛋白的表达,流式细胞仪检测人外周血CD4＋T的表达。结果血液中SHP-2的表达在宫颈癌组明显高于CIN组与正常宫颈组,差异有统计学意义。血液中CD4＋T的表达在宫颈癌组明显低于CIN组与正常宫颈组,差异有统计学意义。结论宫颈癌组SHP-2高表达,CD4＋T低表达。SHP-2负调控T细胞的激活,使宫颈癌发生成为可能。     

Prevalence of high-risk human papillomavirus infection in different cervical lesion among organized health-examination women in Shanghai, China

Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.     

组织芯片检测MCM2和HPV16在宫颈癌中的表达及意义

目的：探讨MCM2和HPV16在宫颈癌组织中的表达及相关性。方法：采用免疫组化ABC法检测MCM2和HPV16在不同病变宫颈组织芯片中的表达。结果：MCM2在宫颈癌中表达高于正常宫颈,有显著性差异（P〈0.05）,HPV16在宫颈癌和C IN中表达高于正常宫颈（P〈0.05和P〈0.01）。HPV16表达与病理类型有关,宫颈鳞癌中阳性表达显著高于宫颈腺癌,有显著性差异（P〈0.05）。HPV16与MCM2呈明显正相关（r=0.3608,P〈0.01）。结论：MCM2和HPV16在宫颈癌变过程中起协同促进作用。MCM2是一个敏感、可靠地反映宫颈上皮细胞增殖的指标,其结合HPV的检测对判断宫颈病变的性质及程度有参考价值。     

RELATIONSHIP BETWEEN CYCLIN G1 AND HUMAN PAPILLOMA VIRUS INFECTION IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CARCINOMA

CERVICAL carcinoma has a long time or a rever-sal precursor period: cervical intraepithelial ne-oplasia (CIN)·CIN presents a biological con-tinuum·It is believed that CIN may progress to an invasivedisease, remain steady, or even reverse·1It is very im…     

宫颈癌组织中Survivin、Fas和FasL的表达及其关系

目的检测不同宫颈病变组织中凋亡相关蛋白Survivin、Fas、FasL的表达,分析宫颈癌组织中Survivin与Fas/FasL表达的关系。方法采用免疫组织化学SP法检测47例宫颈癌、25例宫颈上皮内瘤样变（CIN）、20例慢性宫颈炎及20例正常宫颈组织中Survivin、Fas和FasL的表达,分析Survivin、Fas和FasL表达与宫颈癌临床病理特征的关系。采用Spearman秩相关法分析宫颈癌组织中Survivin与Fas/FasL表达的关系。结果 Survivin在宫颈癌组织中的阳性表达率（68.1%）明显高于正常宫颈组织（0%）、慢性宫颈炎组织（15.0%）和CIN组织（36.0%）,差异均有统计学意义（P〈0.05）;Fas在宫颈癌组织中的阳性表达率（48.9%）明显低于正常宫颈组织（90.0%）、慢性宫颈炎组织（85.0%）和CIN组织（80.0%）,差异均有统计学意义（P〈0.05）;FasL在宫颈癌组织中的阳性表达率（93.6%）明显高于正常宫颈组织（0）、慢性宫颈炎组织（50.0%）和CIN组织（68.0%）,差异也均有统计学意义（P〈0.05）。Survivin的表达与宫颈癌临床分期、是否有淋巴结转移有关（P〈0.05）;FasL的表达与宫颈癌的临床分期、病理分级、是否有淋巴结转移有关（P〈0.05）。宫颈癌组织中,Survivin与Fas的表达呈负相关（r=-0.517,P〈0.01）,与FasL的表达呈正相关（r=0.381,P〈0.01）。结论宫颈癌能通过Survivin和FasL高表达及Fas低表达逃避机体免疫监视,促使肿瘤发生、发展及转移。FasL可作为宫颈癌患者病程进展和预后的预测指标之一。