子宫颈上皮内瘤变进展过程中Claudin-1的表达和意义

目前认为,HPV感染与子宫颈癌的发生关系密切,而单独HPV感染并不能引起所感染细胞的恶性转变。除HPV外,其它基因的改变也与子宫颈癌的发生相关．Claudin蛋白属于构成紧密连接的完整膜蛋白家族成员,在不同肿瘤中表达各异Claudin-1在子宫颈癌前病变组织和鳞状细胞癌中表达显著．随着疾病的进展该蛋白表达也同步增强,[第一段]     

子宫颈上皮内瘤变及子宫颈鳞癌中KGF、p16表达及意义

子宫颈鳞癌足常见的妇科恶性肿瘤之一,发病率在女性恶性肿瘤中居第二位。随着子宫颈上支从单纯增生→不典型增生→原位癌→浸润癌的进展,癌变的危险依次升高。而上皮细胞的不典型增生,被认为是子宫颁鳞癌的癌前病变,是组织从正常细胞发展到癌细胞的关键阶段。子宫颈上皮内瘤变（cervical in-traepithelial neoplasia C1N）分为Ⅰ、Ⅱ、Ⅲ级,简称为CINI（轻度不典增生）、CINⅡ（中度不典增生）平和CINⅢ（包括重度小典增生和子宫颈原位痛）,又称为低级别上皮内瘤变（CINⅠ）和高级别上皮内瘤变（包括CINⅡ和CINⅢ）。     

子宫颈上皮内瘤变和子宫颈鳞癌中Twist基因蛋白及Skp2表达

目的 研究Twist和Skp2在子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及子宫颈鳞癌(squamous cell carcinoma,SCC)中的表达及其在癌变中的作用.方法 SP法检测Twist和Skp2在CIN和SCC中的表达,并与正常子宫颈鳞状上皮组对照.结果 正常组、CIN 1级组、CIN 2级组、CIN 3级组及SCC组的Twist和Skp2表达阳性率分别为:0、10%、42.3%、48.3%、52.5%,23.1%、46.5%、73.1%、93.1%和92.5%.Twist和Skp2在正常组与CIN组及SCC组间表达差异有显著性(P<0.005).CIN 1级组与CIN 2级组间表达差异有显著性(P<0.005).结论 Twist和Skp2随着CIN从轻到重至SCC,表达逐渐增强,表明两者在SCC癌变过程中起到协同性作用,共同参与CIN的进展及SCC癌变机制.检测到Twist和Skp2表达增强有助于SCC发生的判断及CIN 1级与CIN 2级分级的临床病理诊断.     

E-Cadherin在子宫颈上皮内瘤变及子宫颈鳞癌中的表达

目的：了解E-Cadherin在子宫颈上皮内瘤变及子宫颈鳞癌的表达及其临床意义。方法：采用S-P免疫组化方法对20例慢性子宫颈炎，40例子宫颈上皮内瘤变及71例浸润性子宫颈鳞癌进行E-Cadherin检测。结果：慢性子宫颈炎、CIN I、CINⅡ、CINⅢ、浸润性子宫颈鳞癌、癌旁组织E-Cadherin的异常表达率分别为40.0%、23.1%、16.7%、60.0%、95.8%及53.8%。子宫颈鳞癌E-Cadherin的异常表达率明显高于子宫颈上皮内瘤变及癌旁组织。结论：CINⅢ、浸润型子宫颈鳞癌E-Cadherin表达下调或缺失。     

子宫颈上皮内瘤变进展过程中Claudin-1、3、4、7的表达及意义

目的探讨紧密连接蛋白Claudin-1、3、4、7在子宫颈正常组织、子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)(包括CIN1、2、3)及浸润性鳞状细胞癌组织中的表达变化及意义。方法应用免疫组化SP法检测9例正常子宫颈组织、12例CIN1、15例CIN2、28例CIN3和22例浸润性鳞状细胞癌组织中Claudin-1、3、4、7的表达。结果从正常子宫颈组织→CIN1/2→CIN3→浸润性鳞状细胞癌,Claudin-1、3、4、7的表达逐渐增加。CIN3及浸润性鳞状细胞癌组织与正常组织及CIN1/2比较,差异有统计学意义(P<0.05)。CIN3与浸润性鳞状细胞癌比较,差异无统计学意义(P>0.05)。Claudin-1与Claudin-7、Claudin-3与Claudin-4的表达强度随疾病的进展呈明显正相关。结论 Claudin-1、3、4、7可能与子宫颈鳞状上皮的恶性转化相关,联合检测Claudin-1、3、4、7的表达可作为CIN和子宫颈鳞状细胞癌早期诊断的辅助指标。     

MCM4、p53在子宫颈上皮内瘤变和子宫颈癌中的表达及其临床意义

目的探讨MCM4和p53在子宫颈上皮内瘤变和子宫颈癌中的表达及其临床意义。方法采用免疫组化EliVision两步法检测48例子宫颈癌、15例CIN1、27例CIN2～3及15例正常子宫颈黏膜上皮组织中MCM4和p53蛋白的表达,并结合临床资料进行分析。结果 MCM4、p53在正常子宫颈黏膜上皮、CIN1级、CIN2～3级与子宫颈鳞癌中表达阳性率分别为6.67%、20.00%、55.56%、83.33%和0、6.67%、18.52%、41.67%,差异均有显著性(P0.05)。MCM4的表达与子宫颈鳞癌的病理学分级和临床分期有关(P0.05),与年龄分组和淋巴结转移无关(P0.05)。p53的表达与子宫颈鳞癌的病理学分级、临床分期、年龄分组和淋巴结转移均无相关(P0.05)。MCM4和p53表达无相关(P0.05)。结论 MCM4可以作为细胞增殖标志,用于子宫颈癌及其癌前病变的鉴别和诊断,并可评估肿瘤预后,指导临床治疗。     

子宫颈癌及上皮内瘤变中cyclin E与Rb蛋白表达的意义

子宫颈鳞状细胞癌（cervical squamous cell carcinoma,CSCC）是女性生殖系统常见的恶性肿瘤。宫颈鳞状细胞周期调节失控及癌基因空谈与CSCC密切相关。cyclin E和Rb基因均与细胞周期调节有关,其异常表达在许多人类肿瘤中存在,但在CSCC癌变过程中的作用及其意义研究较少。我们利用免疫组化方法探讨CSCC癌变过程中cyclin E和Rb蛋白的表达,以期寻找CSCC癌变机制及其对CSCC的诊断等方面的意义。     

基因表达谱芯片在预测子宫颈上皮内瘤变进展风险中应用

目的利用基因芯片技术筛选出与预测子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)发展成子宫颈癌危险性相关的差异表达基因。方法收集3例病理诊断为子宫颈癌的新鲜标本,分为正常组、CIN1、CIN2/3及子宫颈癌4组(共12个样本),利用Illumina Bead Chip平台对其进行全基因组表达谱分析。结果与正常组相比,CIN1组中有41个上调基因,105个下调基因;CIN2/3组中有57个上调基因,16个下调基因;子宫颈癌组中有1 137个上调基因,513个下调基因。在CIN1和CIN2/3中有13个基因(ANKRD20A1、OLFM4、SNORD46、LOC642333、C13orf30、ASB5、C6、CABP4、POU5F1P1、DNHD2、LR-RC50、C1orf87和CCDC17)共同上调,4个基因(DEFB103B、IL6、CDC45L和E2F2)共同下调。而ANKRD20A1、DEFB103B和IL6在CIN1、CIN2/3和子宫颈癌各组中均共同上调或下调。结论在子宫颈癌发生的早期阶段,ANKRD20A1、OLFM4、SN-ORD46、LOC642333、C13orf30、ASB5、C6、CABP4、POU5F1P1、DNHD2、LRRC50、C1orf87及CCDC17等基因的上调具有重要作用。对上述差异基因的检测可能对评估CIN病变尤其是CIN1发展为子宫颈癌的危险性具有帮助,从而减少由于子宫颈病变的异质性和子宫颈活检技术的局限性所导致的CIN2/3漏诊,同时指导临床医师对CIN1进行更合理的管理和治疗。     

子宫颈上皮内瘤变的临床诊断治疗相关进展

子宫颈癌是妇女生殖系统最常见的恶性肿瘤,起源于子宫颈上皮内瘤变,筛查发现子宫颈上皮内瘤变并积极治疗是预防子宫颈癌有效的措施。本文从子宫颈上皮内瘤变的高危因素及病理分型诊断入手,探讨子宫颈上皮内瘤变的诊断与治疗的相关进展。     

子宫颈鳞状细胞癌中IMP3表达与MVD的相关性分析

目的：分析子宫颈鳞状细胞癌(squamous carcinoma of the cervix, SCC)中胰岛素样生长因子域 mRNA结合蛋白3(insu-lin-like growth factor 域mRNA binding protein 3, IMP3)表达与微血管密度(microvessel density, MVD)的相关性。方法采用免疫组化SP法检测正常子宫颈( normal cervical epithelium, NCE)、低级别子宫颈上皮内瘤变( low-grade cervical intraepithelial ne-oplasia, CIN-L)、高级别子宫颈上皮内瘤变( high-grade cervical intraepithelial neoplasia, CIN-H)和 SCC 组织中 IMP3表达及MVD值,并分析二者与SCC的关系。结果(1) IMP3在NCE、CIN-L、CIN-H和SCC组织中的阳性率分别为0(0/15)、0(0/11)、37.5%(9/24)和86.0%(43/50),差异有统计学意义(字2=53.345,P=0.000);与NCE组相比,CIN-H、SCC组中IMP3阳性率差异均有显著性(P<0.0083);与SCC组相比,CIN-L、CIN-H组中IMP3阳性率差异均有显著性(P<0.0083);(2)子宫颈组织中MVD值随子宫颈病变的进展而增高,差异有统计学意义(F=145.968,P<0.01),各组之间MVD值差异亦具有显著性(P<0.05);(3)SCC组织中IMP3阳性率及MVD值与肿瘤分化程度、肌层浸润深度及淋巴结转移有关(P<0.05),与患者年龄无关(P>0.05),SCC组织中IMP3表达与MVD值具有相关性(rs =0.323,P<0.05)。结论 IMP3在SCC的发生、浸润和转移过程中起重要作用,其异常表达可能与肿瘤的微血管形成有关。     

Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma

HECD-1 monoclonal antibody has been used to localize E-cadherin, a calcium-dependent cell–cell adhesion molecule, in microwave-treated, paraffin-embedded sections from 53 cases of cervical intraepithelial neoplasia (CIN) (11 CIN I, 22 CIN II, and 20 CIN III), 16 invasive cervical squamous cell carcinomas, and seven metastases. In normal cervix, E-cadherin was expressed on the cell membrane of basal and parabasal cells. Cytoplasmic staining was present in occasional basal cells only. In CIN, the presence and localization of cytoplasmic E-cadherin were found to be significantly correlated with the grade of the CIN lesion. In squamous cell carcinomas, reduced membranous and increased cytoplasmic staining was seen with worsening differentiation. Loss of membranous E-cadherin expression was also detected in 4/7 metastatic deposits. E-cadherin expression (120 kD form on Western blotting) was seen in human cervical carcinoma cell lines (HT3, ME180, C41, Caski) that maintained the ability to aggregate in a homotypic adhesion assay and showed a typical epithelial morphology. E-cadherin-negative cell lines (Hela, SiHa, C33A) did not show adhesion. HOG-1 was the only E-cadherin-negative cell line which showed a significant degree of cell–cell aggregation. These data indicate that loss of membranous E-cadherin expression may represent one of the abnormalities underlying loss of cell polarity and differentiation which characterize CIN and invasive cervical cancer.     

VEGF在宫颈上皮内瘤样病变及宫颈癌的表达及意义

目的探讨血管内皮生长因子（VEGF）在宫颈上皮内瘤样病变（CIN）及宫颈癌中的表达及意义。方法采用免疫组织化学SP法检测22例正常子宫颈、24例CIN、44例子宫颈癌石蜡标本组织中VEGF蛋白的表达情况。结果VEGF蛋白在正常宫颈、CIN、宫颈癌中的阳性表达率分别为45.45%、83.33%、95.45%,差异有非常显著意义（P〈0.01）。正常子宫颈与CIN比较、CIN与宫颈癌比较,VEGF蛋白的表达量均有显著性差异（P〈0.01）。结论VEGF蛋白在宫颈癌的发生中有一定作用,提示这种蛋白有可能作为高危人群早期筛查的一种免疫组化指标。     

Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma

Claudins (CLDNs), of which 24 types have been identified, are integral transmembrane proteins of the tight junctions that are critical for maintaining cell adhesion and polarity. They also act as selective barriers. Cells and tissues are characterized by individual CLDN patterns; the composition and levels of expression change during differentiation and tumor formation. Alterations in the expression of individual CLDNs have been detected in several carcinomas and shown to be related to progression and invasion; however, their role in carcinogenesis is controversial. Using a panel of polyclonal (CLDNs 1, 3, and 7) and monoclonal (CLDNs 2 and 4) antibodies, CLDN pattern and expression were studied by immunohistochemistry in 105 cervical tissue specimens, including normal epithelia (n = 20), cervical intraepithelial neoplasias (CINs; CIN 1/2, n = 27; CIN 3, n = 10), carcinoma in situ (CIS, n = 15), and 33 squamous keratinizing and nonkeratinizing invasive carcinomas. No CLDN 3 was observed in normal or intraepithelial neoplastic cells, but significantly increased expression of CLDNs 1, 2, 4, and 7 was detected in the CIN/CIS lesions and invasive carcinomas compared with the normal tissues (P < .001) and reduced reactivity of CLDNs 1 and 2 was observed in invasive cervical cancers compared with CIN 3/CIS (P = .0001) and of CLDNs 2, 4, and 7 compared with CIN 1/2. These results indicate increased expression of CLDNs in the early phase of carcinogenesis in intraepithelial lesions, which decreases during progression to invasive disease. Expression of CLDN 1 was strongest in premalignant stages; thus, it may serve as a good diagnostic marker for the detection of CIN.     

子宫颈鳞状细胞癌中DLC-1和Cyclin D1的表达及其相关性分析

目的 观察肝癌缺失基因-1(deleted in liver cancer-1,DLC-1)和Cyclin D1在正常子宫颈组织、子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及子宫颈鳞状细胞癌(cervical squamous cell carcinoma,CSCC)中的表达,并探讨二者与CSCC临床病理参数间的关系.方法 应用免疫组化SP法及逆转录-聚合酶链反应法(RT-PCR)检测DLC-1和Cyclin D1在正常子宫颈组织、CIN及CSCC中的表达,采用统计学软件SPSS 19.0对数据进行分析.结果 (1)DLC-1在正常子宫颈组织、CIN及CSCC中的阳性率依次降低,其表达与CSCC的肿瘤分级、FIGO分期及淋巴结转移有关,结合RT-PCR结果,差异具有统计学意义(P＜0.05);(2) Cyclin D1在正常子宫颈组织、CIN和CSCC中的阳性率依次升高,其表达与CSCC的肿瘤分级、FIGO分期及淋巴结转移有关,结合RT-PCR结果,差异具有统计学意义(P ＜0.05);(3) DLC-1和Cyclin D1在CSCC中的表达呈负相关(r=-0.526,P＜0.001).结论 DLC-1低表达和Cyclin D1高表达与CSCC的发生、发展和侵袭、转移相关,二者联合检测可作为CSCC诊断、治疗的重要判断指标.     

CD34(+) fibrocytes in normal cervical stroma,cervical intraepithelial neoplasia III,and invasive squamous cell carcinoma of the cervix uteri

CD34(+) fibrocytes are widely distributed in normal connective tissues but have been reported to be absent within the stroma associated with invasive carcinomas. In the present study we investigated the presence and distribution of CD34(+) fibrocytes and alpha-smooth muscle actin (alpha-SMA) positive myofibroblasts in cervical intraepithelial neoplasia III (CIN III; n=8), invasive carcinoma of the cervix ( n=18) and adjacent normal cervical stroma. Normal cervical stroma and the stroma adjacent to CIN III disclosed a dense network of CD34(+) fibrocytes, whereas the stroma of invasive carcinoma was virtually free of this cell population. Early stromal invasion by squamous carcinoma was characterized by a focal loss of CD34(+) fibrocytes. alpha-SMA-positive myofibroblasts were not seen in the normal cervical stroma but occurred in six of eight cases of CIN III adjacent to the atypical epithelium. The stroma of invasive carcinoma was made up of large amounts of haphazardly arranged alpha-SMA-positive myofibroblasts. In the setting of the present study, a loss of CD34(+) fibrocytes was specific for stromal alterations associated with invasive carcinoma and proved to be a sensitive tool in detecting small foci of stromal invasion. Therefore, detection of a loss of CD34(+) fibrocytes may constitute an adjunctive tool in detecting (1) early stromal invasion and (2) invasive carcinoma in small biopsy specimens. Moreover, the present study shows that CD34(+) fibrocytes and myofibroblasts play an important role in stromal remodeling associated with invasive squamous cell carcinoma of the cervix.     

宫颈上皮内瘤变及宫颈鳞癌中cyclin D1、Ki-67的表达及其意义

目的： 检测细胞周期素D1（cyclin D1）、增殖细胞核抗原（Ki-67）在人乳头瘤病毒（HPV）感染患者宫颈上皮内瘤样病变（CIN）及宫颈鳞癌中的表达及其相关性,研究其在CIN及宫颈鳞癌发生及发展过程中的作用。方法: 研究组HPV阳性病理确诊CINⅠ17例、CINⅡ19例、CINⅢ23例、宫颈鳞癌23例,对照组HPV阳性病理确诊柱状上皮异位22例。应用免疫组化S-P法检测宫颈病变组织中cyclin D1、Ki-67蛋白的表达,杂交捕获二代检测宫颈分泌物中HPV感染的情况。结果: (1)Cyclin D1在5组宫颈组织细胞的细胞核内均有表达,CINⅢ组、宫颈鳞癌组与对照组比较差异显著（P<0.05）,CINⅢ组、宫颈鳞癌组与CINⅠ组比较差异显著（P<0.05）,宫颈鳞癌组与CINⅡ组比较差异显著（P<0.05）。(2)Ki-67在5组宫颈组织细胞的细胞核内均有表达,对照组与CINⅢ组比较差异显著（P<0.05）,对照组与宫颈鳞癌组比较差异显著（P<0.05）,CINⅠ组与宫颈鳞癌组比较差异显著（P<0.05）,CINⅡ组与宫颈鳞癌组比较差异显著（P<0.05）。(3)Cyclin D1、Ki-67在CIN及宫颈鳞癌中的表达强度呈正相关关系 （P<0.05）。结论: Cyclin D1和Ki-67在CIN和宫颈鳞癌发生发展及细胞增殖活动中起一定的作用;两者在CIN和宫颈鳞癌的发生发展中可能发挥协同作用。