PCNA在宫颈鳞癌组织中的表达及意义

目的探讨细胞核增值抗原（proliferating cell nuclear antigen,PCNA）在宫颈鳞癌和宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）组织中的表达及意义。方法采用免疫组织化学S-P法检测92例宫颈鳞癌、40例CIN和92例宫颈正常组织的PCNA蛋白表达情况。结果宫颈鳞癌组织PCNA阳性表达率为82.61%（76/92）;CINⅠ、CINⅡ和CINⅢPCNA阳性表达率分别为33.33%（5/15）、71.43%（10/14）和81.82%（9/11）,正常宫颈组织无PCNA表达。宫颈鳞癌、CINⅡ和CINⅢ组织PCNA阳性表达率明显高于CINⅠ（P〈0.01）;但宫颈鳞癌PCNA表达与CINⅡ、CINⅢ比较,差异无统计学意义（P〉0.05）。PCNA阳性表达与宫颈癌分期（r=0.634,P〈0.01）、组织学分级（r=0.654,P〈0.05）有关;而与年龄无关（r=0,P〉0.05）。结论 PCNA的阳性表达可能与宫颈癌的发生、发展及细胞增殖活性增加有关。     

吲哚胺2,3双加氧酶与妇科肿瘤关系的研究进展

吲哚胺2,3双加氧酶(indoleam ine2,3-d ioxygenase,IDO)是必需氨基酸色氨酸分解代谢的胞内限速酶,在肿瘤介导的免疫抑制方面引起了诸多关注。IDO表达与多种恶性肿瘤的不良预后相关,如子宫内膜癌、卵巢癌、宫颈癌、白血病和大肠癌。了解IDO的作用机制及反作用原理,为妇科肿瘤的临床治疗提供新的思路,具有积极的实用价值与临床意义。     

宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义北大核心CSCD

目的探讨宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义。方法选取2015年1月至2017年10月河北省承德医学院附属医院保存的宫颈癌组织58例,宫颈上皮内瘤变(CIN)组织47例,正常宫颈组织43例,采用免疫组化染色检测C-Fos、PDGFR蛋白阳性表达,western blot检测C-Fos、PDGFR蛋白表达量。结果宫颈癌组织C-Fos和PDGFR蛋白阳性表达率分别为58.62%和62.07%,C-Fos和PDGFR蛋白表达量分别为(0.987±0.221)和(0.872±0.206),明显高于CIN和正常宫颈组织(P <0.05);CIN组织C-Fos和PDGFR蛋白阳性表达率分别为21.28%和27.66%,C-Fos和PDGFR蛋白表达量分别为(0.344±0.157)和(0.550±0.214),明显高于正常宫颈组织(P <0.05);Ⅲ～Ⅳ期宫颈癌C-Fos和PDGFR蛋白表达量分别为(1.012±0.220)和(1.012±0.220),明显高于Ⅰ～Ⅱ期宫颈癌(P <0.05);中低分化宫颈癌PDGFR蛋白表达量为(0.892±0.184),明显高于高分化宫颈癌(P <0.05);宫颈癌组织C-Fos和PDGFR蛋白表达量无相关性(P>0.05)。结论宫颈鳞癌组织C-Fos、PDGFR蛋白表达明显高于CIN和正常宫颈,与临床分期和分化程度具有一定的相关性,可能在宫颈癌发生过程中发挥一定的作用。     

吲哚酸2,3-二氧化酶与妊娠相关疾病

吲哚胺2,3-二氧化酶(indoleamine2,3-dioxygenase,IDO)是肝脏以外唯一可催化色氨酸(Trp)经犬尿氨酸途径代谢的限速酶,γ干扰素(IFN-γ)能激活IDO,导致Trp缺乏,可抑制免疫细胞尤其是T细胞增殖.IDO主要表达在抗原提呈细胞和胎盘滋养细胞,在诱发宿主免疫防御、诱导母胎免疫耐受和神经系统调节中均发挥重要的免疫调节作用.就IDO和自然流产、子痫前期、感染性妊娠并发症和产后抑郁症等妊娠相关疾病的关系进行综述.     

半乳凝素-3在宫颈上皮内瘤变及宫颈鳞状细胞癌中的表达及其意义

目的:探讨半乳凝素-3(Galectin-3)在宫颈上皮内瘤变(CIN)及宫颈鳞状细胞癌(SCC)中的表达及其意义。方法:选择经病理确诊为CIN和SCC患者的石蜡标本60例,以同时期因子宫肌瘤行全子宫切除患者的正常宫颈组织(NC)石蜡标本10例作为对照,采用免疫组化方法分析CIN及SCC中Galectin-3表达情况。结果:NC、CIN、SCC及SCCⅠ、SCCⅡ、SCCⅢ组Galectin-3表达阳性率分别为40.00%、50.00%、83.33%及70.00%、90.00%、90.00%。NC、CIN、SCC3组间Galectin-3表达阳性率差异有统计学意义(χ2=9.559,P=0.049);NC组Galectin-3表达阳性率与SCCⅡ期组及Ⅲ期组比较,差异有统计学意义(χ2=5.495,P=0.029)。宫颈肿瘤>2cm组Galectin-3表达阳性率高于≤2cm组,差异有统计学意义(χ2=4.690,P=0.047)。结论:SCC中Galectin-3的阳性表达与肿瘤大小有关;Galectin-3表达阳性率随宫颈病变发展而升高。Galectin-3可能在SCC的发生、进展中发挥作用。     

PHD2在宫颈病变中的表达及意义

目的:研究不同宫颈组织中脯氨酸羟化酶2(PHD2)的表达情况,初步探讨PHD2在宫颈病变中的作用和意义。方法:选取正常宫颈、CINⅠ和CINⅡ、CINⅢ、宫颈癌标本各20例,应用逆转录多聚酶链反应(RT-PCR)、免疫组化法(SP法)检测PHD2 mRNA和蛋白水平的相对表达情况。结果:正常宫颈、CINⅠ和CINⅡ、CINⅢ、宫颈癌组织中,PHD2蛋白和mRNA表达水平依次上调,两两比较差异均有统计学意义(P0.01)。结论:PHD2可能参与宫颈病变的发生发展,作为肿瘤标记物用于早期诊断和预后判断。下调PHD2的高表达,可能成为治疗宫颈癌的新靶点。     

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。     

宫颈上皮内瘤变及鳞癌诊治过程中病理分级及治疗探讨

目的探讨宫颈上皮内瘤变(CIN)及鳞状细胞癌(鳞癌)活检、锥切或全子宫切除术后病理分级及转化.方法对2003年1月至2006年9月CIN及鳞癌病例,行不同诊治手段,对比分析病理分级及其转化.结果经阴道镜活检,病理证实CIN 217例,平均年龄38.9岁;鳞癌62例,平均年龄53.3岁.其中继续锥切诊治63例,直接子宫全切54例.转阴率、分级转低率、分级不变率和分级转高率分别为14.5%、19.7%、59.0%和6.8%.结论本组活检诊断与锥切术后病理分级符合率仅59.0%,说明CIN为多点病变,分级变异性较大,活检甚至锥切不能代表真实病变.而且子宫全切术后转阴率较低,且有6.8%的分级转高率.应注意加大锥切的范围,增加其诊疗效果.     

FasL在宫颈鳞癌和宫颈上皮内瘤变的表达及其在肿瘤逃逸机制中的作用

恶性细胞逃逸免疫系统有几种机制，其一是通过表达FasL。为探讨Fas/FasL在宫颈癌及其癌前病变引起的免疫细胞凋亡从而逃脱免疫监视的作用，取自人宫颈癌和正常宫颈的石蜡包埋组织，宫颈癌细胞株为美国流行病控制中心（ATCC）和国际肿瘤学会（NCI）提供。石蜡包埋组织切片后，按实验操作说明分别进行免疫组化、免疫荧光末端脱氧核糖核酸转移酶生物-dUTP缺口端标记染色。     

存活素、细胞周期蛋白D1在宫颈上皮内瘤变及宫颈鳞癌中的表达及意义

子宫颈癌是常见的妇女恶性肿瘤之一，有关宫颈癌研究一直是妇科肿瘤工作者关注的问题。存活素（surviwin）是一种凋亡抑制基因，可抑制细胞凋亡，同时survivin基因的表达具有细胞周期依赖性，在细胞分裂过程中起重要作用。细胞周期G1期（细胞第一生长期）中cyclinDl对于GI／s转折点有重要的作用。为深入探讨宫颈癌的发生发展机制，本研究探讨survivin、cyclinDl在宫颈癌发生发展中的作用，为阐明宫颈癌发病机制和临床治疗肿瘤提供依据。     

Prognostic Significance of Pretreatment Squamous Cell Carcinoma Antigen and Carcinoembryonic Antigen in Squamous Cell Carcinoma of the Uterine Cervix

Sixty-seven patients with squamous cell carcinoma of the uterine cervix (FIGO Stages IB2, IIA, and IIB) were reviewed to evaluate the pretreatment level of squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) which may be used to predict a subset of patients with poor prognosis. The rate of pathologic pretreatment serum level of SCC increased significantly in cases with Stage IIB compared to that of Stages IB2 and IIA (50% versus 16.3%). The rate of pathologic pretreatment serum level of CEA did not show any difference between these two groups (29.2% versus 30.2%). The 48-month disease-free survival for patients with pathologic pretreatment serum levels for one or both tumor-associated antigens (TAAs) was 40.0% versus 91.7% for patients with normal levels (log-rank test,P< 0.005) in Stages IB2 and IIA. Patients who had a pathologic pretreatment serum level for one or both TAAs showed higher incidence of lymph node metastasis than patients with normal levels (36.7% versus 10.8%). The patients who had pathologic pretreatment serum levels for both TAAs and lymph node metastasis have the poorest prognosis. The pretreatment serum levels for one or both TAAs make it possible to predict the clinical response to neoadjuvant chemotherapy consisting ofcis-platinum (DDP) and 5-fluorouracil (5-FU). Our findings suggest that pretreatment of SCC in conjunction with CEA is a valuable tumor marker to predict the prognosis of squamous cell carcinoma of the uterine cervix and to foresee a clinical response to subsequent neoadjuvant chemotherapy.     

Langerhans Cell Population in Early Invasive Squamous Cell Carcinoma Of The Uterine Cervix

Langerhans cell counts were performed using indirect immunoperoxidase staining for S100 protein in 10 cases of early invasive squamous cell carcinoma of the cervix and 20 controls from routine hysterectomy specimens. There was a significant (p < 0.01) reduction in the number of Langerhans cells per unit sectional area of tumour tissue compared to the normal cervical epithelium. The density of Langerhans cells in the 3 patients with tumour metastasis in pelvic lymph nodes was further reduced. The low density of Langerhans cells in invasive squamous cell carcinoma compared to the normal state may reflect poor local immunosurveillance and may be related to progression and spread of the tumour.     

A Case of Polymyositis and Invasive Squamous Cell Carcinoma of the Uterine Cervix

Summary: To our knowledge, this is the fifth reported case of invasive cervical neoplasia associated with idiopathic inflammatory myopathy and illustrates the importance of cervical examination in women with polymyositis.     

Prognostic Significance of Epithelial–Stromal Vascular Cuffing and Microvessel Density in Squamous Cell Carcinoma of the Uterine Cervix

Objective. Tumor angiogenesis has been shown to play an important role in tumor growth and metastasis. This study examines the prognostic significance of two histological markers of angiogenesis, i.e., vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, and microvessel density (MVD), the number of microvessels in a unit area, in cervical squamous cell carcinoma.Methods. One hundred twenty-two specimens from surgically resected uteri with cervical squamous cell carcinoma were histologically reviewed and immunostained for CD34. VC was graded into “none,” “incomplete,” and “complete.” The MVD was determined by counting the microvessels with a light microscope within a ×200 field area where neovascularization occurred most actively. Stromal inflammation was also split into three grades. The relationship of VC or MVD to clinicopathological prognostic factors such as FIGO stage, cervical stromal invasion, lymph–vascular space invasion, pelvic lymph node metastasis, and parametrial invasion was evaluated using univariate and multivariate analyses.Results. The patients with a complete VC pattern showed a significantly worse prognosis compared to those with a pattern graded as either none or incomplete (P < 0.011 and P < 0.0001, respectively). The Cox regression analysis revealed the complete VC pattern, together with parametrial invasion, to be an independent prognostic indicator for overall survival. MVD and the grading of stromal inflammation showed no significant relationship with VC or overall survival.Conclusions. The complete VC pattern may therefore be a useful prognostic indicator in cervical squamous cell carcinoma.     

Differential Transforming Growth Factor-β Secretion in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix

Tumor cells from eight freshly isolated cervical cancers (i.e., four adenocarcinomas and four squamous carcinomas) were analyzed for their production of the immune-inhibitory cytokine transforming growth factor-β (TGF-β)in vitro.All fresh adenocarcinomas secreted significant levels of TGF-β (mean 397, range between 207 and 782 pg/ml/10⁵cells/48 hr). In contrast, no detectable TGF-β was present in the supernatants from the four fresh squamous carcinoma cultures (P< 0.001). These data suggest that major differences in the secretion of the immunoinhibitory cytokine TGF-β exist between squamous cell carcinomas and adenocarcinomas of the uterine cervix. Furthermore, these findings suggest that at least some of the differences in the natural biologic behavior, as well as in the response to radiation treatment, between these two histologic types of cervical cancer could be related to differences in secretion of this immune-inhibitory cytokine.     

Indoleamine 2,3-dioxygenase,immunosuppression and pregnancy

Pharmacologic inhibition of indoleamine 2,3-dioxygenase (IDO) activity during murine pregnancy results in maternal T-cell-mediated rejection of allogeneic but not syngeneic conceptuses. Increased risk of allogeneic pregnancy failure induced by exposure to IDO inhibitor is strongly correlated with maternal C3 deposition at the maternal-fetal interface. Here we review evidence that cells expressing IDO contribute to immunosuppression by inhibiting T-cell responses to tumor antigens and tissue allografts, as well as fetal tissues.     

宫颈鳞癌组织中PD-ECGFmRNA与PD-ECGF的表达及临床意义

目的:研究PD ECGF与宫颈鳞癌发生与发展的关系及作用机制。方法:采用原位杂交和免疫组化法,对87例宫颈鳞癌和2 3例正常及慢性宫颈炎组织PD ECGFmRNA、PD ECGF蛋白进行检测。结果:①PD ECGF在宫颈鳞癌细胞及间质细胞中均有表达,表达率分别为6 2 .0 7%、2 3.2 0 %。PD ECGFmRNA主要在宫颈鳞癌细胞中表达,表达率为5 7.4 7%。二者与宫颈鳞癌临床分期、组织分化程度明显相关(P <0 .0 5 )。②一致性检测发现宫颈鳞癌组织中PD ECGF基因的免疫组化与原位杂交检测结果关系密切(P <0 .0 1 )。结论:①PD ECGF由宫颈鳞癌细胞产生,在间质内发挥作用。②PD ECGF与宫颈鳞癌的发生、发展有密切关系,可作为判断宫颈鳞癌生物学行为和预后的重要指标。     

Establishment and Characterization of a New HPV-Negative Squamous Cell Carcinoma Cell Line (Yumoto) from the Human Uterine Cervix

A new cell line, Yumoto, derived from a squamous cell carcinoma of the uterine cervix, was established from serially transplanted tumor tissues in nude mice. Monolayer cultured cells were polygonal and formed pavement-like sheet. They showed a piling-up tendency and were devoid of contact inhibition. Electron micrographs demonstrated the presence of microvilli on the cell surface, abundant tonofilaments in the cytoplasm, and the connection with desmosomes. These electron micrographical characteristics of Yumoto cells were consistent with those of squamous cell origin. Yumoto cells were highly tumorigenic in BALB/c nude mice and produced a well-differentiated squamous cell carcinoma of keratinizing type which closely resembled to the original tumor tissues in nude mice. The presence of HPV DNA was examined using polymerase chain reaction and Southern blot analysis, but no known types of HPV DNA could be detected. Exons 2 through 11 of the p53 gene were analyzed by direct DNA sequencing, revealing a homozygous mutation at codon 281 in exon 8, GAC to CAC (Asp→His). Furthermore, physical p53-gene deletion was demonstrated by dual-color fluorescencein situhybridization. This cell line is useful for studying the carcinogenesis of cervical carcinoma and for investigating the biological characteristics of a HPV-negative and mutated p53 squamous cell carcinoma of the uterine cervix.