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。     

子宫颈鳞状细胞癌中PDHA1的表达及临床意义

目的 探讨丙酮酸脱氢酶E1亚单位α(pyruvate dehydrogenase E1 component subunit alpha,PDHE1α)(又称PDHA1)在子宫颈鳞状细胞癌(cervical squamous cell carcinoma,CSCC)中的表达及临床意义.方法 采用免疫组化EnVision法...     

子宫颈鳞状细胞癌中SIAH2蛋白表达的临床意义

目的 探讨SIAH2表达与子宫颈鳞状细胞癌临床病理特征和患者预后的关系.方法 采用免疫组化法检测癌旁正常子宫颈组织、高级别鳞状上皮内病变及子宫颈鳞状细胞癌组织中SIAH2的表达,统计分析SIAH2与子宫颈鳞状细胞癌临床病理特征的关系.应用RT-qPCR和Western blot法检测子宫颈新鲜组织中SIAH2 mRNA...     

子宫颈鳞状细胞癌中GDF-15与EMT相关蛋白的表达及相关性

目的检测子宫颈鳞状细胞癌组织中GDF-15及上皮-间质转化(epithelial-mesenchymal transition, EMT)相关蛋白E-cadherin、N-cadherin、vimentin的表达,探讨GDF-15在子宫颈鳞状细胞癌发生、侵袭中的生物学作用。方法采用免疫组化EliVision两步法检测85例子宫颈鳞状细胞癌组织及其配对癌旁子宫颈组织中GDF-15、E-cadherin、N-cadherin、vimentin的表达,分析GDF-15表达与子宫颈鳞状细胞癌临床病理特征的关系及GDF-15与EMT相关蛋白表达的相关性。结果与癌旁子宫颈组织相比,子宫颈鳞状细胞癌组织中GDF-15、N-cadherin和vimentin表达上调,E-cadherin表达下调,差异有统计学意义(P均0.05)。子宫颈鳞状细胞癌组织中GDF-15表达与N-cadherin和vimentin表达呈正相关(r_s=0.422,r_s=0.374),与E-cadherin表达呈负相关(r_s=-0.305)。结论 GDF-15与EMT相关蛋白在子宫颈鳞状细胞癌组织中异常表达,过表达GDF-15在子宫颈癌的发生、侵袭中发挥重要作用,可能与诱导子宫颈癌EMT有关。     

子宫颈鳞状细胞癌组织中MCT4的表达及其临床病理学意义

目的探讨单羧酸转运蛋白4(monocarboxylate transporters 4,MCT4)在子宫颈鳞状细胞癌组织中的表达及其临床病理学意义。方法采用免疫组化SP法分别检测72例子宫颈鳞状细胞癌组织和48例子宫颈正常组织中MCT4的表达,分析其表达与子宫颈鳞状细胞癌临床病理特征的关系。结果 MCT4在子宫颈鳞状细胞癌组织中的阳性率为81.9%(59/72),明显高于子宫颈正常组织(35.4%,17/48),两组相比差异有统计学意义(χ2=26.848,P<0.001)。MCT4表达与子宫颈鳞状细胞癌临床分期(χ2=5.389,P=0.020)和淋巴结转移(χ2=4.706,P=0.030)有关,与患者年龄(χ2=1.238,P=0.266)、肿瘤分化程度(χ2=0.530,P=0.467)及浸润深度(χ2=1.300,P=0.254)无关。结论 MCT4在子宫颈鳞状细胞癌组织中高表达,且与临床分期和淋巴结转移密切相关,有望成为子宫颈鳞状细胞癌生物行为的有效指标之一。     

子宫颈鳞状细胞癌中Stat3和PTEN的表达及意义

目的 探讨转录信号传导子与激活子3(Stat3)和抑痛基因PTEN在子宫颈鳞癌、子宫颈上皮内瘤变组织及正常子宫颈组织中的表达及临床病理意义.方法 采用免疫组化方法 检测了58例子宫颈鳞癌组织,37例CIN组织,17例正常子宫颈组织中Stat3和PTEN的表达.结果 Stat3在子宫颈鳞癌、CIN Ⅱ～Ⅲ、CIN Ⅰ和正常子宫颈组织中阳性表达率分别为70.7%、33.3%、13.6%和5.9%.Stat3在子宫颈浸润癌中的表达高于正常对照组、CIN Ⅰ及CIN Ⅱ～Ⅲ(P均<0.05).Stat3在子宫颈鳞癌的表达与病理分级、临床分期及淋巴结转移有关(P值均<0.05).PTEN在子宫颈鳞癌中阳性表达率为34.5%,在正常子宫颈组织中阳性表达率为88.2%,两者差异有显著性(P<0.01).PTEN在淋巴结未转移组中阳性表达率明显高于淋巴结转移组(P<0.01).PTEN表达与临床分期呈负相关,而与患者年龄、病理分级无相关性(P均>0.05).子宫颈鳞癌中Stat3与PTEN表达成负相关(rs=-0.375,P<0.01).结论 Stat3的过表达和PTEN的失活在子宫颈鳞癌的发生、发展及转移过程中发挥重要作用,二者联合检测可作为子宫颈良、恶性病变早期病理诊断的辅助指标.     

子宫颈鳞状移行细胞癌临床病理分析

目的 分析子宫颈鳞状移行细胞癌（squamotransitional cell carcinoma,STCC）的临床、病理及免疫组化表达特征,探讨STCC的诊断和鉴别诊断及细胞分化。方法 参照2003年WHO子宫颈肿瘤组织学分类,对8例STCC进行临床病理形态学观察和免疫组化检测。结果 患者平均年龄37．1岁（28～54岁）,临床表现为接触性阴道出血,部分病例白带有异味,病程1个月～5年。子宫颈肥大呈粗颗粒状或微绒状,部分病例（2／8）见息肉或菜花样新生物。所有病例均见乳头状结构,乳头由多层异型鳞状细胞样或移行细胞样上皮覆盖,细胞无挖空特征,乳头内为纤维血管中心柱;大部分乳头为非浸润性,2例为浸润性,2例子宫颈壁有深部浸润的表面乳头中见厚壁血管。所有病例均见程度不等的子宫颈间质浸润（0．1cm至全层）,HE切片下判断4例有脉管内浸润,1例盆腔淋巴结有转移。免疫组化染色显示p16均呈强阳性表达,CK7、CK14、CK19呈不同程度阳性表达,CK20仅在2例见局灶阳性,在D2-40标记下发现6例有淋巴管浸润。结论 STCC是一种具有独立形态学特征的子宫颈恶性肿瘤,有别于子宫颈普通鳞癌及其他呈乳头状生长的恶性肿瘤如疣性癌、疣状癌等;尽管大部分乳头为非浸润性,STCC易向子宫颈壁浸润的特点提示深部活检明确诊断的必要性,乳头内厚壁血管可能与深部浸润有关;免疫组化结果提示STCC属鳞状细胞癌,不支持有真正的移行细胞分化。STCC与高危型HPV感染有关,易经淋巴道转移。     

酸性磷酸酶染色特性及阳性细胞鉴别诊断

宫颈癌在现代女性所患恶性肿瘤中位居第二,如果宫颈癌能及早发现,它属于极易治愈的癌症之一。宫颈癌筛查目前被认为是控制宫颈癌发病的最有效手段,可以降低宫颈癌的发病率和死亡率。目前的宫颈癌筛查是采用薄层液基制片技术联合巴氏染色,受多因素影响,这种方法有一定的局限性。酸性磷酸酶检测是一种新近应用于子宫颈异常细胞筛查的化学染色及细胞学检测方法,其检测原理是宫颈异常细胞中酸性磷酸酶活力升高,利用化学染色方法在有酸性磷酸酶活性的细胞内形成红色沉淀。本文分析了酸性磷酸酶染色阳性细胞的特征以及与TCT-巴氏染色样本进行对比观察,提出酸性磷酸酶染色的细胞学诊断标准及报告方式。     

子宫颈HPV相关性乳头状鳞状细胞癌的临床病理分析

目的 探讨子宫颈乳头状鳞状细胞癌(papillary squamous cell carcinoma, PSCC)的临床病理学特征、诊断及鉴别诊断。方法 收集18例子宫颈PSCC临床资料,行HE和免疫组化染色,分析其临床病理特征,并复习相关文献。结果 18例患者年龄30～71岁,平均49岁,镜下活检和手术标本均可见浅表乳头状结构,伴纤维血管轴心,被覆上皮具有子宫颈高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion, HSIL)的特征。17例子宫颈活检病理学检查均为典型的PSCC,1例子宫颈虽有菜花样肿物,但活检标本未见间质浸润,行子宫颈锥切,锥切标本仍未见间质浸润。13例行根治性子宫切除,最后均诊断为子宫颈PSCC,伴间质浸润;4例活检诊断后失访。免疫表型：p16呈弥漫强阳性(块状)染色,p63、CK7阳性,CK20阴性,Ki-67增殖指数>90%,遍布上皮全层。14例行HPV DNA分型检测,其中10例HPV 16阳性(71.4%),2例分别合并HPV 53和HPV 59感染。结论 子宫颈PSCC具有典型的病理形态学表现,...     

Acid phosphatase in squamous cell carcinoma

Surgical specimens of oral squamous cell carcinoma were processed for cytochemistry of acid phosphatase using Gomori's substrate. Reaction product was deposited in the cytoplasmic dense bodies, autophagic vacuoles, cytoplasmic projections, and advancing cell borders. Results of this study suggest that acid phosphatase and its associated lysosomes seem to play a role in the invasiveness of cancer cells.     

Increased carcinoembryonic antigen expression in cervical intraepithelial neoplasia grade 3 and in cervical squamous cell carcinoma

Carcinoembryonic antigen (CEA) is a highly glycosylated cell surface protein that is overexpressed in a variety of human tumors and has been used as a tumor marker for disease progression in colorectal cancer patients. Recently, CEA has been used as a target for vaccine therapy against advanced CEA-expressing colonic adenocarcinomas. Previous reports have found elevated serum CEA levels in patients with cervical cancer, although this did not correlate with disease progression. In this study, cervical biopsy specimens from patients with normal histology, cervical intraepithelial neoplasia (CIN) grades 1 to 3, cervical squamous cell carcinoma (SCC), and adenocarcinoma were evaluated for CEA expression by immunohistochemistry by using the monoclonal antibody COL-1. Staining intensity was graded on a scale of 0 to 3 and was correlated with histologic diagnoses. CEA staining intensity was significantly increased in high-grade squamous lesions (CIN III and SCC) compared with normal cervical mucosa and CIN grades I or II (P <.0001). There was a linear correlation between grade of lesion and staining intensity (r = 0.71). CEA expression increased most significantly between CIN grades 2 to 3. Only 1 of 7 primary cervical adenocarcinomas expressed CEA. Only 1 of 10 patients with high CEA expression in their tumors by immunohistochemistry had elevated serum CEA. We thus have shown that lesional CEA expression increases in CIN 3 and SCC without elevations in serum CEA. CEA expression may be a useful diagnostic tool and a useful marker for identifying those at risk for progressive cervical neoplasia. HUM PATHOL 31:1357-1362.     

子宫颈、食管鳞状细胞癌人乳头状瘤病毒感染的比较研究

目的 探讨同一地区人乳头瘤病毒在宫颈鳞状细胞癌的感染特征及与食管鳞状细胞癌的关系.方法 采用PCR技术和快速导流杂交基因芯片技术分别对来自河南同一地区的75例宫颈鳞癌患者和78例食管鳞癌患者进行HPV 分型检测.结果 来自同一地区的宫颈、食管鳞癌组织中,HPV16型阳性检出率均最高,分别为83%(58/70)和82%(49/60),其余阳性类型宫颈鳞癌中依次为HPV58、18、31、6、52、33、11,分别占14%(10/70),9%(6/70),7%(5/70),6%(4/70),6%(4/70),4%(3/70),4%(3/70);食管鳞癌中依次为HPV18、58、31、6、11,分别占15%(9/60),8%(5/60),7%(4/60),5%(3/60),5%(3/60).对HPV16阳性的宫颈、食管鳞癌标本DNA进行HPV16致癌基因E6/E7扩增进行验证,阳性率为100%.结论 同一地区居民宫颈(食管)鳞癌HPV感染亚型相似,提示HPV可能是这两种肿瘤的共同致病因素,HPV16可能在宫颈和食管癌变过程中起重要作用,也为其生物防治提供了重要理论依据.     

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。     

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.     

SNIP1在宫颈鳞状细胞癌中的表达及意义

目的:探究Smad核内相关蛋白1(Smad nuclear interacting protein 1,SNIP1)在正常宫颈上皮组织及宫颈鳞状细胞癌(宫颈鳞癌)组织中的表达及其意义.方法:免疫组织化学方法及实时荧光定量PCR(Real-time PCR)技术检测SNIP1在23例正常宫颈组织(正常宫颈组)、25例早期宫颈鳞癌组织(Ⅰ a～Ⅱa期)(早期宫颈鳞癌组)和45例晚期宫颈鳞癌组织(Ⅱb～Ⅲb期)(晚期宫颈鳞癌组)中的表达.结果:免疫组织化学方法显示SNIP1蛋白在正常宫颈组、早期宫颈鳞癌组及晚期宫颈鳞癌组中胞质强阳性表达率分别为0,36.0％和73.3％;胞核强阳性表达率分别为17.4％,44.0％和71.1％,且三组间胞质与胞核的表达差异均具有统计学意义(P＜0.01).在伴有淋巴结转移的宫颈鳞癌病例中,SNIP1在胞质、胞核中的强阳性率分别高于不伴淋巴结转移病例,且差异有统计学意义(P＜0.001).Real-time PCR技术检测显示SNIP1 mRNA在正常宫颈组、早期宫颈鳞癌组及晚期宫颈鳞癌组中表达呈递增趋势,除了正常宫颈组与早期宫颈鳞癌组间差异无统计学意义外,其余各组间差异有统计学意义(P＜0.05).结论:SNIP1可能参与调控宫颈鳞癌的进展及侵袭转移过程的发生,并有望成为宫颈鳞癌侵袭转移情况的预测因子.     

HPV感染和p53异常表达与宫颈鳞癌的关系

目的研究宫颈鳞癌与p53蛋白表达和HPV感染的关系,探讨宫颈鳞癌的形成机制。方法采用RT-PCR法分别检测p53基因在39例宫颈鳞癌组织和39例正常宫颈黏膜组织中的表达情况以及PCR方法检测HPV在这些组织中的感染情况。结果 HPV在宫颈鳞癌组中阳性率为48.72%(19/39),正常组织中为14.81%(4/27),p53基因表达在宫颈鳞癌组中阳性率为53.85%(21/39),正常组织中为18.52%(5/27),宫颈癌组的HPV感染和p53表达均高于正常组(P0.05)。结论 HPV感染与p53基因的异常表达与宫颈鳞癌发生密切相关,联合检测能提高准确性。     

Identification of microRNA expression signature for the diagnosis and prognosis of cervical squamous cell carcinoma

Cervical cancer is the fourth leading cause of cancer death among women globally. The prognosis of cervical cancer patients differs considerably, and clinical outcomes are difficult to predict. Given the significant roles of miRNAs in human cancers, identification of novel and reliable miRNA biomarkers is important for targeted cervical cancer therapy. In the present study, we aimed to reveal biological significance of miR-200a, miR-423, miR-34a, miR-193a, and miR-455 for the prognosis and diagnosis of cervical cancer and their association with the clinical outcomes of patients. Distinct expression profiles of miRNAs in formalin-fixed paraffin-embedded tissue samples of patients and healthy controls were evaluated using qRT-PCR. We identified miR-200a, miR-455, and miR-34a were significantly downregulated in cervical squamous cell carcinoma tissues compared to normal cervix tissue from healthy controls. Both miR-455 and miR-34a confer a promising diagnostic factor for the cervical cancer while miR-200a showed no significance in ROC analysis. Notably, low expression of miR-34a was markedly associated with the poor overall survival of cervical cancer patients as revealed by Kaplan-Meier survival analysis. Also, univariate and multivariate analysis indicated miR-34a expression as an independent prognostic factor. Consequently, our results underline the importance of distinct expression miRNAs in cervical squamous cell carcinoma.