口腔粘膜上皮癌变过程中增殖细胞核抗原改变研究

采用抗增殖细胞核抗原单克隆抗体对５８例标本进行了免疫组化染色，结果显示：正常口腔粘膜基底细胞层可有少量ＰＣＮＡ阳性细胞，而上皮异常增生及鳞癌时，随着病变程度的加重，ＰＣＮＡ阳性表达也相应提高，统计学分析，各组间有显著差异（Ｐ＜０．０５）。提示：ＰＣＮＡ表达对判断口腔癌前病变的增殖活动有一定意义。     

DMBA诱导的金黄地鼠颊囊癌变粘膜中增殖细胞核抗原表达

实验采用抗增殖细胞核抗原单克隆抗体对１０９例金黄地鼠颊囊粘膜标本作免疫组化染色及网格计数和形态学观察，发现正常的金黄地鼠颊囊粘膜基底层有少量增殖细胞核抗原（ＰＣＮＡ）阳性细胞，而上皮异常增生以及癌变时，随着病变程度的加重，ＰＣＮＡ阳性细胞率也相应增加。统计学分析显示：正常粘膜各级上皮异常增生以及癌变各组间ＰＣＮＡ阳性细胞率有显著差异（Ｐ＜０．０５），轻度上皮异常增生组中涂ＤＭＢＡ６周与７周的ＰＣＮＡ阳性分级有显著性差异（Ｐ＜０．０５）；涂ＤＭＢＡ７周，８周，９周之间，其ＰＣＮＡ阳性分级无差异（Ｐ＞０．０５），提示ＰＣＮＡ可作为动态观察癌前病变过程中细胞增殖程度的一种检测指标，它的敏感性强于光镜形态学观察。     

口腔粘膜癌变过程中表皮生长因子受体表达水平

采用ＡＢＣ免疫组化染色体图像分析技术，检测了口腔粘膜异常增生及鳞癌中表皮生长因子受体（ＥＧＦＲ）表达情况。正常口腔粘膜中，ＥＧＦＲ仅见于上皮基层和近基层，粘膜异常增生时，ＥＧＦＲ表达范围随异常增生程度加重而扩展到上皮棘层及表层，鳞癌时几乎所有细胞均有ＥＧＦＲ超量表达，但染色程度不均，图像进一步表明，从正常粘膜，轻，中重异常增生粘膜的鳞癌，细胞中ＥＧＦＲ相对含量呈现显著递增，由此提示，ＥＧＦＲ表达与     

口腔扁平苔藓病变中增殖细胞核抗原和DNA的检测

目的：探讨ＰＣＮＡ表达在反映口腔扁平苔藓及癌变组织增殖的可行性及临床意义。方法：应用Ｓ－Ｐ免疫组化法检测ＰＣＮＡ在口腔扁平苔藓、扁平苔鲜上皮异常增生及鳞癌组织中的表达；应用图像分析仪检测上述组织中ＤＮＡ含量的变化；用统计学方法分析ＰＣＮＡ与ＤＮＡ的相关关系。结果：随着病变程度的增加，ＰＣＮＡ的增殖指数增加，ＤＮＡ倍体逐渐增多，各组间有显著性差异。统计学检验证实ＰＣＮＡ与ＤＮＡ倍体值间有相关关系，ｒ＝０．８１５。结论：ＰＣＮＡ的表达可以反应病变细胞的增殖活性，在口腔扁平苔藓病变中有一定的应用价值     

实验性口腔癌发生过程中增殖细胞核抗原表达的研究

目的：利用金黄地鼠颊癌模型,探讨口腔癌发生过程中增殖细胞核抗原（ＰＣＮＡ）表达变化及其规律。方法：０．５％二甲基苯并蒽（ＤＭＢＡ）丙酮液处理地鼠颊粘膜,每周３次,３、６、９和１２周分批处死动物;对照组不处理。利用抗ＰＣＮＡ单克隆抗体,免疫组化方法（ＬＳＡＢ）检测ＰＣＮＡ的表达情况。结果：正常地鼠颊粘膜ＰＣＮＡ表达主要位于基底层和少数棘层细胞,３周单纯增生类似正常,６～９周上皮呈不同程度异常增生,ＰＣＮＡ表达扩展至棘层,甚至全层,与异常增生程度呈正相关;１２周鳞癌形成时,ＰＣＮＡ表达明显增加,且见明显异质性。结论：ＤＭＢＡ诱导地鼠颊癌发生过程中存在ＰＣＮＡ异常表达,且与癌变进展有关,提示ＰＣＮＡ表达可作为口腔癌变监测的生物学标志之一。     

实验性口腔癌发生过程中增殖细胞核抗原表达的研究

目的：利用金黄地鼠颊癌模型，探讨口腔癌发生过程中增殖细胞核抗原（ＰＣＮＡ）表达变化及其规律。方法：０．５％二甲基苯并蒽（ＤＭＢＡ）丙酮液处理地鼠颊粘膜，每周３次，３、６、９和１２周分批处死动物；对照组不处理。利用抗ＰＣＮＡ单克隆抗体，免疫组化方法（ＬＳＡＢ）检测ＰＣＮＡ的表达情况。结果：正常地鼠颊粘膜ＰＣＮＡ表达主要位于基底层和少数棘层细胞，３周单纯增生类似正常，６￣９周上皮呈不同程度异常增生，Ｐ     

口腔粘膜上皮癌前及癌变中PCNA和P53的表达

目的：检测口腔粘膜上皮癌前及癌变组织中ＰＣＮＡ和ｐ５３的表达，探讨口腔癌变的机理。方法：采用免疫组化的方法检测８０例口腔粘膜病变组织中ＰＣＮＡ和ｐ５３的表达。结果：正常口腔粘膜基底层有少数ＰＣＮＡ阳性细胞，随着粘膜异常增生程度的加重到鳞癌，ＰＣＡＮ表达的阳性分级升高，ＰＣＮＡ的相对含量也升高。Ｐ５３的阳性表达仅见于重度异常增生及鳞癌组织中。结论：对ＰＣＮＡ和ｐ５３的研究有助于探讨口腔粘膜癌变多阶段发生过程的机理，并可为监测癌变提供生物学指标。     

口腔鳞癌增殖细胞核抗原表达及其临床意义

目的：检测口腔鳞状细胞癌中增殖细胞核抗原（ＰＣＮＡ）的表达，探讨与鳞癌预后相关的因素。方法：采用免疫组化的方法，利用ＰＣＮＡ的单克隆抗体检测４４例口腔鳞癌组织中ＰＣＮＡ的表达。结果：低分化鳞癌较高分化鳞癌ＰＣＮＡ的表达明显增强（Ｐ＜０．０５）；晚期鳞癌中ＰＣＮＡ阳性细胞百分率比早期鳞癌显著增高（Ｐ＜０．０５）；ＰＣ－ＮＡ高表达者的淋巴结转移倾向大于ＰＣＮＡ低表达者。结论：ＰＣＮＡ标记可以作为判断鳞癌预后的参考指标。     

口腔粘膜白斑增殖细胞核抗原的研究

采用抗增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｌｎｕｃｌｅａｒａｎｔｉｇｅｎ，ＰＣＮＡ）单克隆抗体免疫组织化学方法，对１７例正常口腔粘膜和５０例口腔粘膜白斑及鳞癌进行了观察，结果表明，单纯增生性白斑ＰＣＮＡ阳性分级与正常口腔粘膜差异无显著性（Ｐ〉０．０５）；随着病变程度的加重，异常增生性白斑及鳞癌的ＰＣＮＡ阳必分级相应提高，统计学分析显示各组间差异显著性（Ｐ〈０．０５）。本研究提示，增殖细     

口腔粘膜白斑角蛋白表达的免疫组化研究

口腔白斑是具有恶变倾向的粘膜病变，其恶变潜能取决于发生部位和上皮异常增生的程度，但仅靠常规组织学检查来判断上皮异常增生程度有一定困难。近来的研究表明，口腔上皮的异常增生和分化紊乱往往伴有细胞角蛋白的表达改变。我们采用抗角蛋白单克隆抗体３４ＢＥ１２、ＭＮＦ１１６分别对正常口腔粘膜、单纯白斑和白斑伴上皮异常增生进行免疫组化检测，发现不同类型的口腔粘膜所含的角蛋白组分有一定差异。单纯白斑中角蛋白表达类型与正常粘膜上皮相似，但染色程度增强。白斑伴异常增生时，大分子角蛋白表达减弱，分布不规则，小分子角蛋白表达增强，分布范围增大，随异常增生的程度加重向上皮表层扩展。提示通过对角蛋白组分的检测，可了解病理状态下口腔上皮细胞的增殖情况和分化程度，对区别粘膜上皮单纯增生和癌前病变有辅助性诊断作用。     

增殖细胞核抗原的表达在口腔粘膜上皮癌变诊断中的意义

目的　研究增殖细胞核抗原 ( PCNA)在口腔粘膜上皮癌变过程中的表达及其在癌变诊断中的意义。方法　采用免疫组化 S-P法对正常口腔粘膜、轻中重度粘膜上皮异常增生和高分化鳞癌共 85例标本进行 PCNA检测。结果　正常口腔粘膜基底细胞层可有少量 PCNA阳性细胞 ;而上皮异常增生和鳞癌时 ,随着病变程度加重 ,PCNA阳性表达也相应提高 ,且阳性反应出现在基层以上部位 ;尤其是重度异常增生 ,其 PCNA阳性表达率较中度异常增生明显增强 ( P=0 .0 0 0 8) ,而重度异常增生与鳞癌间 ,PCNA表达无显著性差异 ( P=0 .72 15 )。结论　 PCNA表达在口腔粘膜上皮癌变诊断中有重要参考价值 ,可作为监测其恶性变的重要生物学指标     

Cell proliferation and tumour suppressor gene expression in iodine unstained area surrounding oral squamous cell carcinoma

The purpose of this study was to investigate the relationship between epithelial dysplasia unstained with iodine and the expression of proliferating cell nuclear antigen (PCNA) and/or tumour suppressor gene (p53) and the existence of glycogen. Thirty cases of squamous cell carcinomas arising from the buccal mucosa and floor of the mouth were examined. Iodine unstained areas were diagnosed histopathologically as mild, moderate or severe epithelial dysplasia. Normal oral mucosa stained with iodine was used as a control group. There was no histochemical difference in the distribution or ratio of PAS-positive cells between the control and the mild epithelial dysplasia groups, however PAS stained areas of the moderate and the severe dysplasia groups were significantly decreased. Ultrastructurally, glycogen granules were not recognized in the moderate or severe dysplastic epithelia. Immunoreactive ratios of PCNA and p53 in the moderate and severe dysplastic groups were significantly higher than those of the control and the mild dysplasia groups. The positive ratio of PCNA was higher than that of p53, although the immunostaining patterns of PCNA- and p53-positive cells were quite similar. These results suggest that mild dysplastic epithelia that are stained with iodine may be in the category of normal epithelia, whereas both moderate and severe dysplasia that are un-stained with iodine may be suspected of malignant lesions.     

Upregulation of heme oxygenase-1 in oral epithelial dysplasias

The expression of heme oxygenase-1 (HO-1), stress-related enzyme, is induced in leukaemia and some cancer tissues, but relatively little is known about the differential pattern of HO-1 expression and proliferation in premalignant lesions of the epithelial oral mucosa. The purpose of this study was to evaluate whether HO-1 expression and proliferation were increased in preneoplastic lesions compared to normal and oral cancer tissues. Immunohistochemical staining was used to examine the expression patterns of HO-1 and proliferating cell nuclear antigen (PCNA) in a series of normal mucosa and mild-to-severe cases of oral epithelial dysplasia (OED) and oral squamous cell carcinoma. Both HO-1 and PCNA are expressed in the basal cells of normal oral mucosa. In patients with OED and carcinoma in situ, immunostaining for PCNA and HO-1 was more intense, and gradually extended into the superficial layers of the mucosa. HO-1 and PCNA expression was correlated with the degree of epithelial dysplasia. Oral squamous cell carcinoma also showed elevated expression of HO-1, but this level was not higher than in severe OED or carcinoma in situ. These results suggest that the up-regulation of HO-1 in premalignant oral lesions is part of an early cytoprotection mechanism against carcinogenesis in the oral mucosa.     

Increase in placental glutathione S-transferase in human oral epithelial dysplastic lesions and squamous cell carcinomas

This study investigated the immunohistochemical expression of human placental glutathione S-transferase (GST-φ) in the epithelium of oral premalignant and malignant lesions. Epithelial lining of normal oral mucosa, hyperplastic lesions and oral epithelium exhibiting mild dysplasia showed weak to moderate GST-φ staining. Moderate epithelial dysplasia revealed an increased antibody content while severe dysplasia. carcinoma- in-situ (CIS) and squamous cell carcinoma (SCC) demonstrated markedly increased antibody binding. The GST-φ staining was evident mainly in the cytoplasm. Severe dysplasia. CIS and SCC were also characterized by areas of cells with intensive nuclear GST-φ staining. These findings support the hypothesis that GST-φ plays a role in human oral carcinogenesis and may be used as a tumor marker for human oral premalignant and malignant lesions.     

口腔鳞癌发生过程中Survivin促血管生成作用的研究

目的探讨口腔鳞癌发生过程中Survivin促进血管生成的作用。方法选取北京口腔医院病理科存档石蜡标本45例,其中口腔白斑伴上皮轻-中度异常增生16例,口腔白斑伴上皮重度异常增生12例,口腔高-中分化鳞状细胞癌17例,另取正常口腔粘膜组织10例作对照。采用免疫组化SP法对各组织病损中Survivin和Von Willebrand Factor的表达情况进行检测。结果免疫组化结果显示,从正常粘膜→白斑伴上皮轻-中度异常增生→白斑伴上皮重度异常增生→口腔鳞癌,Survivin的表达量呈增加趋势;微血管密度则由正常对照组的28．49±11．87条／mm^2升高到口腔鳞癌组的91．98±40．20条／mm^2,各组之间有显著性差异。结论Survivin的过度表达是口腔鳞癌发生过程中的早期事件。随着Survivin表达量的增加,微血管密度明显升高。Survivin的过表达可能抑制了血管内皮细胞的凋亡,从而促进血管的生成。     

细胞角蛋白19和间隙连接蛋白43在4-亚基硝氧喹啉诱发大鼠舌黏膜癌变过程中表达的研究

目的 研究4-亚基硝氧喹啉（4NQO）诱发大鼠口腔黏膜癌变过程中细胞角蛋白19（CK19）和间隙连接蛋白43（Cx43）的表达,探讨口腔黏膜癌变过程中CK19与Cx43的相关性。方法 利用4NQO诱导SD大鼠的口腔黏膜癌变,运用免疫组织化学的方法检测CK19、Cx43在口腔黏膜癌变过程中各阶段的动态变化。结果 在大鼠正常舌黏膜组织中,CK19阳性染色的细胞散在分布于黏膜基底层;随着大鼠舌黏膜上皮异常增生程度的增加,CK19表达于黏膜基底上层;在口腔鳞状细胞癌（OSCC）组织中,CK19阳性染色细胞分布在黏膜各层。CK19在正常舌黏膜、轻度上皮异常增生、中度上皮异常增生、重度上皮异常增生、OSCC组织中阳性表达率分别为30.00%、50.00%、58.33%、80.00%、91.67%,差异有统计学意义（P<0.05）。在正常舌黏膜中Cx43蛋白主要表达于大鼠舌黏膜上皮细胞的细胞膜上,上皮的基底层、棘层和颗粒层呈阳性染色。随着大鼠舌黏膜上皮异常增生程度的增加,Cx43的表达明显下降。Cx43在正常舌黏膜、轻度上皮异常增生、中度上皮异常增生、重度上皮异常增生、OSCC组织中阳性表达率分别为100.00%、85.71%、66.67%、40.00%、33.33%,差异有统计学意义（P<0.05）。结论 在大鼠舌黏膜癌变过程中,CK19蛋白表达水平随病变程度加重显著升高,提示CK19与口腔上皮细胞的癌变有关;Cx43蛋白表达水平随病变程度加重显著下降,Cx43表达下降是口腔黏膜癌变的早期事件。CK19与Cx43蛋白表达呈负相关,CK19和Cx43的联合检测对OSCC的早期诊断有重要的作用,有利于提高OSCC早期诊断的灵敏度和特异性。     

口腔粘膜上皮癌变过程表皮生长因子受体的表达及意义

目的 研究口腔粘膜上皮癌变过程中表皮生长因子受体的表达及意义。方法 采用免疫组化Ｓ－Ｐ法对正常口腔粘膜,轻中重度粘膜上皮异常增生和高分发化鳞癌共８５例标本进行ＥＧＦＲ检测。结果 正常口腔粘膜全部为阴性。上皮异常增时,随病变程度加重,ＥＧＦＲ阳性表达也相应提高,至重度异常增生时,阳性表达率达最高峰。而高分化鳞癌时,表达率有所下降。结论ＥＧＦＲ的表达与口腔鳞癌的发生有关,可作为评估口腔上皮恶谱潜能的较     

Assessment of c-Jun, c-Fos and cyclin D1 in premalignant and malignant oral lesions

Some oral cancers are known to develop from dysplastic oral epithelium. In the present study, the expression of c-Jun, c-Fos, and cyclin D1 proteins in oral epithelial lesions with different degrees of dysplasia, and in oral squamous cell carcinomas (OSCCs) was evaluated. Eighteen cases of mild dysplasia, 23 cases of moderate to severe dysplasia and 24 OSCCs were studied immunohistochemically. Additionally, 15 sections of oral mucosa without any evidence of dysplasia were included in the study. Results: c-Jun expression increased according to the degree of oral dysplasia, with the greatest expression found in OSCC. c-Fos expression was intense in normal mucosa, reduced in mild dysplasia and high in moderate to severe dysplasia and in OSCCs. Cyclin D1 was expressed in only a few cases of moderate to severe dysplasia and in most of the OSCCs. Statistical analysis showed a correlation between the three proteins and the degree of epithelial alteration. The present results indicate a possible role of c-Jun and c-Fos in malignant transformation of oral mucosa.     

Aktuelle Klassifikation der Präkursorläsionen des oralen Plattenepithelkarzinoms

The WHO classification of oral tumours summarizes the precancerous squamous cell lesions under the term epithelial precursor lesions. For the first time three classification schemas that histologically categorize oral epithelial precursor lesions are used analogously. According to the WHO suggestion of 2005 the traditional schema of grading dysplasia as mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in situ continues to be used. In addition the concept of intraepithelial neoplasia is introduced as squamous intraepithelial neoplasia I-III. Squamous intraepithelial neoplasia III (SIN III) combines severe dysplasia and carcinoma in situ. The Ljubljana classification of squamous intraepithelial lesions was originally established to grade laryngeal epithelial precancerous lesions. The clear and succinct nomenclature and the simple clinical utility of the Ljubljana classification have also proven to be useful for oral epithelial precursor lesions: squamous cell (simple) hyperplasia; basal/parabasal cell hyperplasia (analogous to mild dysplasia and to SIN I); atypical hyperplasia (analogous to moderate-severe dysplasia and to SIN I-III and is also called risky epithelium); carcinoma in situ (analogous to WHO carcinoma in situ and to SIN III). Atypical hyperplasia (risky epithelium) and carcinoma in situ are defined as lesions requiring either total excision or close clinical monitoring.