HPV感染与宫颈上皮内瘤变

宫颈上皮内瘤变(CIN)是与宫颈浸润癌密切相关的一组癌前病变,常可反映宫颈癌发生发展的连续过程.根据Richar的定义,CINⅠ相当于轻度不典型增生,CINⅡ相当于中度不典型增生,CINⅢ相当于重度不典型增生和原位癌.人乳头状瘤病毒(HPV)是宫颈鳞状上皮内病变或宫颈上皮内肿瘤和宫颈癌发病的重要因素.研究发现,99.7%以上的宫颈癌组织中可检测HPV,由高危型HPV感染引起的CIN易发生癌变.     

宫颈上皮内瘤变、宫颈癌中乙酰肝素酶的表达及意义

目的 探讨乙酰肝素酶在宫颈黏膜上皮内瘤变与宫颈癌中的表达及其意义.方法 采用免疫组化SP法检测乙酰肝素酶在56例宫颈黏膜上皮内瘤变(轻度12例,中度26例,重度18例)、54例宫颈癌(伴有淋巴结转移的20例,不伴淋巴转移34例)中的表达.结果 乙酰肝素酶在宫颈黏膜上皮轻、中、重度上皮内瘤变组织中表达率分别为33.33%,38.48%,44.44%,宫颈癌中表达率为48.14%.乙酰肝毒酶在宫颈黏膜上皮内瘤变与宫颈癌中的表达无统计学意义(P＞0.05).20例宫颈癌伴淋巴结转移者,乙酰肝素酶表达(70.00%)明显高于无转移组(35.29%),P＜0.01.结论 乙酰肝素酶表达与宫颈癌发生、发展无关,与宫颈癌组织淋巴结转移有关.     

液基薄层细胞学联合阴道镜在宫颈病变中的应用价值

目的探讨液基薄层细胞学检测(TCT)联合阴道镜下宫颈活检在宫颈病变中的临床应用价值。方法选择近年来在本院接受宫颈病变筛查的患者1685例,所有患者均行TCT检测,细胞学分类采用TBS分类标准,对其中128例TCT检查阳性者行阴道镜下多点活检。结果细胞学异常阳性检出率为7.60%(128/1685),其中不典型鳞状上皮细胞(ASCUS)56例(3.32%),低度鳞状上皮内瘤变(LSIU)42例(2.49%),高度鳞状上皮内瘤变(HSIU)26例(1.54%),宫颈鳞癌(SCC)3例(0.18%),宫颈腺癌(ACC)1例(0.06%)。阴道镜下病理诊断慢性炎症48例,轻度不典型增生(CINⅠ)41例,中度不典型增生(CINⅡ)17例,重度不典型增生及原位癌(CINⅢ)18例,宫颈鳞癌3例,宫颈腺癌1例。结论 TCT检查应用于宫颈病变的筛查,明显提高了宫颈病变的阳性检出率,联合阴道镜检查及镜下活检,能提高宫颈病变的诊断率,及时发现宫颈早期病变及癌变。     

宫颈上皮内瘤变的诊治进展：HPV感染与宫颈上皮内瘤变

宫颈上皮内瘤变（CIN）是与宫颈浸润癌密切相关的一组癌前病变,常可反映宫颈癌发生发展的连续过程。根据Richar的定义,CINⅠ相当于轻度不典型增生,CINⅡ相当于中度不典型增生,CINⅢ相当于重度不典型增生和原位癌。人乳头状瘤病毒（HPV）是宫颈鳞状上皮内病变或宫颈上皮内肿瘤和宫颈癌发病的重要因素。研究发现,99．7％以上的宫颈癌组织中可检测HPV,由高危型HPV感染引起的CIN易发生癌变。     

胃癌及癌前病变组织中PTEN蛋白的表达及意义

采用免疫组化ABC法对10例正常胃黏膜、16例胃黏膜轻度异型增生、12例中度异型增生、14例重度异型增生、16例早期胃癌及52例进展期胃癌组织中的PTEN蛋白进行了检测.结果显示,正常胃黏膜PTEN蛋白阳性表达率为90.0%,轻、中、重度异型增生胃黏膜分别为81.3%、75.0%、42.9%,早期及进展期胃癌分别为37.5%和36.5%.PTEN蛋白在轻度异型增生胃黏膜中的阳性表达率与重度异型增生、早期及进展期胃癌相比,P均<0.05;中度异型增生与早期及进展期胃癌相比,P均<0.05;肠型胃癌的阳性率(50.0%)与弥漫型胃癌(25.0%)相比,P<0.05;淋巴结转移胃癌的阳性率(14.8%)与未转移者( 51.2%)相比,P<0.05.认为PTEN蛋白在胃黏膜癌变过程中发挥了一定作用,可作为判断胃癌预后的一个有用指标.     

胃癌和胃癌前病变中环氧合酶-2、p16的表达及其临床意义

背景：密切监测胃癌前病变是预防和及早发现胃癌的关键。目的：观察胃癌及其癌前病变中环氧合酶-2（COX-2）、p16的表达,探讨两者对胃癌早期诊断的意义。方法：以免疫组化染色检测20例正常胃黏膜、60例肠化生、60例上皮内瘤变和60例胃癌组织中COX-2和p16的表达,并分析两者的相关性。结果：正常胃黏膜、肠化生、上皮内瘤变和胃癌组织中的COX-2表达呈递增趋势,p16表达呈递减趋势。高级别上皮内瘤变和早期、进展期胃癌组织COX-2、p16表达阳性率与正常胃黏膜和肠化生组织相比差异有统计学意义（P〈0.05）,而前三者之间以及后两者之间无明显差异。COX-2、p16表达阳性率在小肠化生、完全型大肠化生与不完全型大肠化生之间以及早期与进展期胃癌之间无明显差异,但在高级别与低级别上皮内瘤变中差异有统计学意义（P〈0.05）。COX-2表达与p16表达呈负相关（P〈0.001）。早期胃癌组织中COX-2表达阳性同时p16表达阴性的比例显著高于高级别上皮内瘤变组织（P〈0.05）。结论：COX-2、p16或两者联合检测有助于监测和随访胃癌前病变、筛选胃癌高危人群,为胃癌的早期诊断提供了重要的检测方法。     

食管早癌的内镜诊断

食管癌的死亡率较高,其预后与早期发现、早期诊断密切相关.通常将食管鳞状上皮重度异型增生和原位癌定义为癌前病变,无淋巴结转移的黏膜内癌和黏膜下癌（即T1 N0M0期）定义为早期食管癌.根据食管、胃肠上皮性肿瘤Vienna分类,将原位癌和重度异型增生归类于高级别黏膜内瘤变,轻度和中度异型增生归类于低级别黏膜内瘤变.     

胃癌、胃黏膜不典型增生和胃炎组织中p185和p21蛋白的表达及其临床意义

目的研究胃癌、胃黏膜不典型增生和胃炎组织中c-erbB-2和ras癌基因产物p185和p21蛋白的表达,以探讨p185和p21蛋白在胃癌发生、发展过程中的作用。方法采用免疫组化S-P法检测39例胃癌组织、24例胃黏膜不典型增生组织和33例胃炎组织p185和p21蛋白的表达。结果p185蛋白在慢性胃炎、轻度胃黏膜不典型增生组织中不表达;在中、重度胃黏膜不典型增生组织中的表达率分别为11.8%和66.7%,差异有显著性(P<0.05),表达程度明显增强(P<0.05);在高、中、低分化胃癌组织中的表达率分别为77.8%、50.0%和29.2%,差异有显著性(P<0.05),高分化胃癌组织中p185蛋白的表达程度明显高于中、低分化胃癌组(P<0.05)。p21蛋白在胃黏膜不典型增生及胃癌组织中的表达率和表达程度较慢性胃炎组明显增高,差异有显著性(P<0.01);在轻、中、重度胃黏膜不典型增生组织中的表达率分别为25.0%、82.4%和100.0%,差异有显著性(P<0.05),表达程度明显增强(P<0.05);在高、中、低分化胃癌组织中的表达率分别为44.4%、66.7%和95.8%,差异有显著性(P<0.01),表达程度明显增强(P<0.05)。p185和p21蛋白在胃癌组织中的表达呈负相关(r=-0.450,P<0.01)。结论c-erbB-2和ras癌基因产物p185和p21蛋白在胃癌致病机制中起重要作用,p21蛋白作用于胃癌发生的早期阶段,p185蛋白可能作用于胃癌发生的较晚期。     

幽门螺杆菌L型感染与食管癌及癌前病变中bcl-2表达关系的研究

目的研究幽门螺杆菌L型(HpL)感染对食管癌及癌前病变凋亡调节基因bcl2蛋白表达的影响,探讨Hp-L在食管癌发生发展过程中可能的致癌机制。方法应用免疫组化和革兰染色技术检测51例食管鳞状细胞癌(原位癌16例,浸润癌35例)及69例鳞状上皮增生性病变(单纯增生15例,轻、中、重度不典型增生分别为21例、18例、15例)和20例正常食管粘膜鳞状上皮组织中HpL型和bcl2蛋白的表达情况,对HpL型阳性和阴性组织的bcl2蛋白表达进行比较分析。结果不同组织类型HpL型检出率在中、重度不典型增生、原位癌、浸润癌均比较高(55.6%～62.9%),与正常组相比均有显著性差异(P<0.005)。在120例食管病变组织中,61例HpL型阳性者的bcl2蛋白表达阳性有48例,占78.7%;79例HpL型阴性者的bcl2蛋白表达阳性24例,占40.7%,两者比较有显著性差异(P<0.005)。各病变组中HpL型感染阳性组的bcl2蛋白表达阳性率高于HpL型阴性组的bcl2蛋白表达阳性率,其差异均有显著性(P<0.005～P<0.025)。表明HpL型感染与bcl2蛋白表达存在着相关性。结论HpL型可能通过影响bcl2蛋白表达,使食管粘膜上皮细胞凋亡调控异常而涉及食管癌的发生发展过程。     

新疆哈萨克族食管病变人乳头瘤病毒-L1衣壳蛋白表达差异性研究

目的探讨人乳头瘤病毒(human papillomavirus,HPV)L1衣壳蛋白在新疆哈萨克族食管病变中的表达差异性及临床意义。方法收集2015年1月至2016年12月在新疆维吾尔自治区人民医院经胃镜检查获得的100例哈萨克族食管病变标本,采用HC2二代杂交捕获法检测HPV DNA,其中56例为阳性,阳性标本采用CytoReact HPV L1试剂盒检测壳蛋白在食管脱落细胞中的表达,并追踪其相对应的病理结果,依据病理学结果进行分组,其中食管炎组32例,低级别上皮内瘤变组3例,高级别上皮内瘤变组6例,食管鳞状细胞癌组15例。结果 56例患者HPVL1壳蛋白的总阳性率为42.8%(24/56),其中食管炎、低级别上皮内瘤变,高级别上皮内瘤变和食管鳞状细胞癌HPVL1壳蛋白的阳性表达率分别为62.5%(20/32)、66.7%(2/3)、33.3%(2/6)、0(0/15)。炎症组及低级别上皮内瘤变组HPV-L1衣壳蛋白阳性率明显升高,高级别上皮内瘤变组及食管鳞状细胞癌组HPV-L1衣壳蛋白阳性率明显下降。食管鳞状上皮癌组与炎症组、低级别上皮内瘤变组及高级别上皮内瘤变组阳性率比较差异有统计学意义(P值分别为0.000 05、0.000 7、0.000 09),炎症组与低级别上皮内瘤变组二者间阳性率差异无统计学意义(P0.05),低级别上皮内瘤变组与高级别上皮内瘤变组阳性率比较差异无统计学意义(P0.05)。结论 HPVL1壳蛋白在新疆哈萨克族食管病变中的阳性表达随病变程度的加重而呈下降趋势,表达存在差异性,提示其有望成为预测新疆哈萨克族食管癌前病变的指标之一。     

胃黏膜低级别上皮内瘤变中胃癌检漏的研究

目的探讨胃黏膜低级别上皮内瘤变(low grade intraepithelial neoplasia,LGIEN)中胃癌漏诊的情况。方法胃镜活检病理诊断为LGIEN的190例患者总结内镜下病灶部位和形态分类,并行内镜复查了解胃癌漏诊情况。结果 190例LGIEN患者病灶主要位于胃窦的137例(72.1%)。镜下病灶形态多样,其中糜烂及溃疡98例(51.6%)。190例患者平均随访时间11.7个月,经内镜病理或手术病理证实胃癌14例,HGIEN患者3例,较前加重者占8.95%;其中符合漏诊患者13例(76.5%),符合可能漏诊患者3例(17.6%)。结论胃镜活检病理检查为LGIEN的患者中部分同时存有癌灶,内镜短期、重复检查可减少胃癌漏诊率。     

胃黏膜低级别上皮内瘤变的胃复春联用叶酸治疗及转归研究

目的：探讨胃复春联用叶酸治疗胃黏膜低级别上皮内瘤变及临床转归。方法：收集上海市7所不同等级医院2011年1月至2011年12月经胃镜活组织检查（活检）病理证实的胃黏膜低级别上皮内瘤变患者共198例,应用胃复春联用叶酸的方案进行药物治疗,并进行定期随访及内镜复查,符合指征者行内镜或外科手术治疗及病理学检查,了解其疗效、转归及胃癌漏诊情况。结果：胃黏膜上皮内瘤变病灶主要位于胃窦（66.7%）,镜下表现多样,主要为粗糙糜烂（37.9%）。药物治疗后患者临床症状总改善率为76.3%。最终随访结果显示,胃黏膜上皮内瘤变病灶完全消退47例（23.7%）,病理消退72例（36.4%）,不变55例（27.8%）,进展22例（11.1%）及腺瘤样变2例（1.0%）,总消退率为60.1%。进展患者中符合漏诊者达50.0%。结论：胃复春联用叶酸能有效缓解胃黏膜上皮内瘤变患者的临床症状,部分消退低级别上皮内瘤变。对低级别上皮内瘤变患者进行定期胃镜随访有望早期检出胃癌病灶,部分胃黏膜上皮内瘤变同时存有癌变病灶,内镜短期、重复检查可减少胃癌漏诊率。     

RASAL1基因在胃癌组织中的表达及其临床意义

目的:探讨Ras蛋白激活物类似物-1(RASAL1)基因在胃癌组织中的表达情况及临床意义.方法:应用免疫组织化学SP法分别检测50例正常组织、50例低级别上皮内瘤变组织、50例高级别上皮内瘤变组织+早期胃癌组织及50例进展期胃癌组织中RASAL1基因的表达,并结合其临床病理资料进行综合分析.结果:RASAL1基因在正常...     

Low- and high-grade non-invasive gastric neoplasia (formerly dysplasia): cytological differentiation (gastro-entero-pancreatic antigens) in association with p53 pattern expression

BACKGROUND/AIMS: In order to better define the evolutive potentiality of non-invasive neoplasia (formerly dysplasia) a study of the cytological differentiation and of the behavior of p53 in relation to the clinical progress has been performed. METHODOLOGY: Gastro-entero-pancreatic antigens, p53 and Ki-67 expression were evaluated in 120 cases of epithelial gastric dysplasia: 70 cases of low-grade dysplasia (LGD) and 50 cases of high-grade dysplasia (HGD). For the cytological study four antigens were studied: two of them gastric (pepsinogen C, gastric foveolar M1), one enteric (CAR-5) and one pancreatic (DU-PAN-2). Routinely processed tissue sections of a colon carcinoma known to contain mutant p53 were used as positive controls for p53 immunohistochemistry. For Ki-67 immunohistochemistry, routinely processed tissue sections of normal lymph node and tonsil were used as staining controls. RESULTS: The study of the coexpression of the gastro-entero-pancreatic antigens showed how all cases of non-invasive neoplasia associated with or progressed to gastric carcinoma (GC) were characterized by entero-pancreatic markers and, in particular, in case of LGD p53 expression positivity was evidenced in 66.6% of cases. Ki-67 hyperproliferation is present in 100% of cases. CONCLUSIONS: The cytological study, only if confirmed by wider casuistries, could represent further information in order to better define the follow-up and the therapeutical decisions in case of non-invasive gastric neoplasia therefore, the immunophenotypic study in association with p53 could lead to more personalized therapeutical choices.     

Clinicopathological significance of FHIT protein expression in gastric adenocarcinoma patients

AIM: To investigate the expression of fragile histidine triad(FHIT) protein, and the possible relationship between FHIT expression and clinicopathological indices in gastric carcinoma. METHODS: FHIT protein expression was examined in 76 cases of gastric carcinoma, 58 cases of intraepithelial neoplasia, and 76 cases of corresponding normal mucosae by immunohistochemical method to analyze its relationship to histological grade, clinical stage, metastatic status and prognosis. RESULTS: The FHIT protein expression was positive in 28/76(36.8%) cases of adenocarcinoma tissue, 22/58(37.9%) cases of adjacent dysplastic tissue and 76/76(100%) cases of distal normal gastric mucosa. There was a significant difference in the expression of FHIT protein between cancer or adjacent intraepithelial neoplasia and normal gastric mucosa(P=0.000). FHIT protein expression was found in 64.3%(18/28) of grades Ⅰ and Ⅱ cancers, and 20.8%(10/48) of grade Ⅲ cancers(P=0.000), in 56.3%(18/32) of stages Ⅰ and Ⅱ cancers and 22.7%(10/44) of stages Ⅲ and Ⅳ cancers(P=0.004), and in 63.6%(14/22) of cancers without metastasis but only 25.9%(14/54) of those with metastasis(P=0.003). The significant difference in the expression of FHIT was found between histological grade, clinical stage and metastatic status of cancer. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of FHIT(71 mo) and those without (33 mo, log rank=20.78, P=0.000). CONCLUSION: FHIT protein is an important tumor suppressor protein. Loss of FHIT protein expression may be associated with carcinogenesis, invasion, metastasis and prognosis of gastric adenocarcinoma.     

Interobserver and Intraobserver Bias Exists in the Interpretation of Anal Dysplasia

INTRODUCTION: Natural history of progression from anal intraepithelial neoplasia to invasive carcinoma remains unproven. The risk of progression may be linked to the severity of dysplasia. Important therapeutic decisions are thus based on the severity of anal intraepithelial neoplasia. Consistency and reliability in the interpretation of anal intraepithelial neoplasia are unproven. METHODS: One hundred ninety anal biopsy specimens were identified for review of dysplasia with a six-point grade system from normal to invasive cancer, evidence of human papillomavirus infection, and quality of histology by three pathologists. RESULTS: Results revealed poor to moderate agreement on grading of quality of histology (weighted kappa score, 0.07-0.22), human papillomavirus status (weighted kappa score, 0.24-0.53), and dysplasia (weighted kappa score, 0.38-0.7). Complete agreement between the original pathology and the three pathologists was observed in only 32 percent of cases. Analysis of 86 slides previously read by one of the pathologists revealed only moderate agreement, with a weighted kappa score of 0.64. CONCLUSION: Significant interobserver and intraobserver bias exists in the interpretation of anal intraepithelial neoplasia. These inconsistencies may explain the uncertainty about the natural progression of anal intraepithelial neoplasia and the varied results of surgery reported for anal intraepithelial neoplasia in the literature.     

内镜黏膜下剥离术在治疗胃上皮内瘤变中的应用与评价

目的探讨胃上皮内瘤变行内镜黏膜下剥离术(ESD)的可行性、必要性及疗效。方法对50例内镜下有明确病灶,表现为浅表病变,活检病理为上皮内瘤变的患者,行ESD切除病灶,对比术前术后病理结果,并内镜随访。结果 34例术前活检病理为低级别上皮内瘤变的病灶ESD术后病理诊断为低级别上皮内瘤变22例、高级别上皮内瘤变6例、黏膜内癌4例、黏膜下浅层癌2例。16例术前活检病理为高级别上皮内瘤变的病灶ESD术后病理诊断为慢性炎症肠上皮化生1例、高级别上皮内瘤变5例、黏膜内癌3例、黏膜下层癌7例。结论 ESD治疗内镜下有明确病灶的上皮内瘤变可及时发现早期胃癌,并有效预防胃癌的发生、发展。     

Ki67和PCNA在胃癌中的表达及其临床诊断价值

目的 分析Ki67和PCNA在慢性胃炎组织、上皮内瘤变组织及癌组织中表达的差异,并评价其临床诊断价值.方法 用免疫组织化学方法检测所有标本Ki67及PCNA的表达,其中胃癌27例,慢性胃炎30例,低级别上皮内瘤变32例,高级别上皮内瘤变19例.结果 Ki67与PCNA在慢性胃炎组、低级别上皮内瘤变组、高级别上皮内瘤变组、胃癌组的阳性表达率呈明显递增关系.随着病变加重,强阳性表达显著增多,差异有显著性（P〈0.001）,随着病变加重,阳性表达范围逐渐增大.结论 Ki67和PCNA反映了胃七皮细胞在癌变过程中细胞增殖活性的改变.增殖活性的改变与癌变过程密切相关.检测Ki67和PCNA可作为预测癌变的观察指标.     

Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas

AIM:To understand the implication of GATA-4 and GATA-5 methylation in gastric carcinogenesis.METHODS: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biopsies from 45 outpatients, gastric dysplasia [low-grade gastric intraepithelial neoplasia (GIN), n = 30; indefinite, n = 77], and 80 paired spo- radic gastric carcinomas (SGC) as well as the adjacent non-neoplastic gastric tissues was analyzed by methylation specific polymerase chain reaction (MS...     

Long-term follow-up study of gastric intraepithelial neoplasias: progression from low-grade dysplasia to invasive carcinoma

BACKGROUND AND STUDY AIMS: A gastric intraepithelial neoplasia (IEN) is usually regarded as a precancerous lesion; however, the natural history of the gastric IEN has not been clarified. We aimed to evaluate the progression of dysplasia in gastric IENs. PATIENTS AND METHODS: As a retrospective study, we reviewed 26 gastric adenomas with low-grade dysplasia (LGD) and one with high-grade dysplasia (HGD) from 18 patients. The patients were followed up for a median of 66 months from 1996 to 2004 (mean 58 months, 20-112 months) in Kyungpook National University Hospital. The histological diagnosis was classified according to the Vienna classification. We reviewed clinical (age and sex), morphological (size, color, shape, location in stomach, surface nodularity, and presence of the erosion), and histological (histological diagnosis, infection with Helicobacter pylori, infiltration of inflammatory cells, atrophy, intestinal metaplasia, microscopic erosions, and glandular appearance) characteristics with regard to progression of dysplasia. RESULTS: We found eight IENs of progressive dysplasia (29.6%). One IEN with HGD and three IENs with LGD progressed to invasive adenocarcinoma (category 5). Four gastric IENs with LGD progressed to HGD (category 4). The clinical, morphological, and histological characteristics did not reveal any distinguishable features for progressive dysplasia. CONCLUSION: For the potential risk of progressive dysplasia, gastric IENs should be treated actively using the recently advanced therapeutic endoscopic techniques, regardless of the degrees of dysplasia.