生存素、半胱氨酸天冬氨酸蛋白酶3在口腔癌前病变及口腔癌中的表达

目的 探讨生存素(survivin)、半胱氨酸天冬氨酸蛋白酶3(caspase-3)在口腔癌发生中的作用,以期为口腔癌的监测和治疗提供参考.方法 选取首都医科大学口腔医学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;正常口腔黏膜组织10例.采用免疫组化SP法对生存素、caspase-3的表达进行检测;脱氧核糖核苷酸末端转移酶介导的原位缺口末端标记法对细胞凋亡指数进行检测.结果 生存素表达在正常黏膜、白斑伴上皮轻-中度异常增生、白斑伴上皮重度异常增生及口腔癌中逐渐增加,阳性细胞率分别为(1.05±1.21)%、(6.06 ±4.87)%、(12.49 ±8.41)%和(21.89±10.45)%;caspase-3的表达在3个病例组中逐渐下降,正常对照、白斑伴上皮轻-中度异常增生、白斑伴上皮重度异常增生及口腔鳞状细胞癌组阳性细胞率分别为(12.37 ±5.48)%、(19.51 ±13.15)%、(9.76±7.83)%和(6.08 ±6.91)%;正常对照、白斑伴轻-中度异常增生、白斑伴重度异常增生及口腔鳞状细胞癌组凋亡指数分别为(0.89 ±0.46)%、(1.29 ±0.63)%、(0.65 ±0.40)%和(0.21 ±0.12)%,前3组与口腔鳞状细胞癌组相比差异有统计学意义(P<0.05).结论 生存素在口腔癌的发生过程中起重要作用,随着生存素表达的增加,caspase-3和凋亡指数呈下降趋势;生存索可能通过抑制caspase-3的表达,从而抑制细胞的凋亡,促进口腔癌的发生.     

谷胱苷肽S转移酶在口腔白斑和口腔鳞癌中的表达

目的：对不同增生程度的口腔白斑和鳞癌中ＧＳＴ－π的表达进行研究。方法：用免疫组化ＡＢＣ法,对单纯增生,轻、中度异常增生,重度异常增生和口腔鳞癌患者的组织病理切片,进行免疫组化染色。结果：口腔白斑和口腔鳞癌组织中均有ＧＳＴ－π表达,且随着白斑异常增生程度增高,其表达逐渐增高,其表达程度与白斑异常增生程度有关,在鳞癌组织中表达最高。结论：ＧＳＴ－π可作为口腔白斑和口腔癌的标志物,可对口腔白斑和口腔癌的     

P16在口腔白斑和鳞癌组织中的表达及其意义

目的探讨P16在口腔白斑癌变过程中的变化及其意义。方法免疫组化polymer法检测P16蛋白在口腔白斑和鳞癌组织中的表达情况。结果 P16蛋白在10例正常口腔黏膜组织、16例单纯增生性白斑、10例异常增生性白斑及30例口腔鳞癌组织中表达逐步下降,在正常口腔黏膜组织和单纯增生性白斑中表达强于异常增生性白斑组织和鳞癌组织（P〈0.05）,在异常增生性白斑中表达亦强于鳞癌组织（P〈0.05）。结论 P16蛋白表达下降可以作为口腔白斑癌变的指征之一。     

口腔白斑组织中表皮生长因子受体的表达

本文应用抗表皮生长因子受体（EGFR）多克隆抗体，采用S－P免疫组化方法，对10例正常口腔粘膜组织，20例上皮单纯增生性白斑，14例上皮异常增生性白斑，21例口腔鳞癌组织进行研究。结果提示，口腔白斑组织中EGFR的异常表达与口腔白斑上皮异常增和癌变有关，作者认为EGFR的异常表达可能是口腔白斑恶变的较好的标志。     

人类主要组织相容抗原Ⅰ类分子在口腔白斑中表达的临床意义

目的通过检测人类主要组织相容抗原Ⅰ类分子（MHC-Ⅰ）在伴有不同异常增生程度的口腔白斑中的表达,以探讨MHC-Ⅰ类抗原表达改变后其局部免疫状态的变化,以及与口腔白斑发生的关系。方法应用MHC-Ⅰ特异性单抗通过免疫组织化学方法从蛋白表达水平检测28例正常口腔黏膜、55例口腔白斑、31例口腔鳞癌内MHC-Ⅰ类抗原的表达。结果伴有重度异常增生的口腔白斑与口腔鳞癌内MHC-Ⅰ类抗原的表达显著低于正常口腔黏膜组（P<0.05）。不伴异常增生及伴有轻、中度异常增生的口腔白斑内MHC-Ⅰ类抗原的表达和正常黏膜未见统计学差异（P＞0.05）。结论MHC-Ⅰ在口腔白斑中存在有表达降低的现象,特别在伴有重度异常增生时,其降低与异常增生的程度有关,对判断口腔白斑的预后有一定价值。     

口腔鳞癌组织中Survivin的表达与血管生成的关系

目的 :观察口腔鳞癌组织中Survivin的表达及其与微血管密度 (microvesseldensity ,MVD)的关系 ,探讨Survivin对口腔鳞癌血管生成的作用及意义。方法 :收集口腔鳞癌标本 42例 ,其中有淋巴结转移者 14例 ,正常口腔黏膜组织 10例 ,用免疫组化染色法探测Survivin和CD3 4 的表达情况并计数微血管密度 (MVD)。结果 :正常口腔黏膜均未见Survivin表达 ,口腔鳞癌中Survivin表达阳性率为 80 .95 % ( 3 4/4 2 )。口腔鳞癌中MVD显著高于正常组织 ,且随病理分化不良而增高 (P <0 .0 5 ) ,有淋巴结转移组MVD显著高于无淋巴结转移组 (P <0 .0 5 ) ,Survivin表达阳性组中MVD明显高于Survivin表达阴性组 (P <0 .0 5 ) ,Survivin的表达与MVD呈正相关 (P <0 .0 5 )。结论 :Survivin在口腔鳞癌组织中的高度表达在口腔鳞癌发生发展中起重要作用 ,并与其血管生成和淋巴结转移有关     

口腔黏膜白斑组织转化生长因子-β受体Ⅱ及受体Ⅲ的表达

目的研究转化生长因子-β受体Ⅱ(transforming growth factor type-Ⅱreceptor,TβRⅡ)及转化生长因子-β受体Ⅲ(transforming growth factor type-Ⅲreceptor,TβRⅢ)在口腔黏膜白斑组织中的表达情况。方法应用免疫组织化学技术分析临床收集的25例口腔正常黏膜组织、21例不伴上皮异常增生的口腔白斑组织、24例伴有异常增生的口腔白斑组织中TβRⅡ和TβRⅢ的表达。结果 TβRⅡ弥漫性强阳性细胞数正常组织中为40.0%,白斑不伴异常增生组织中下降到32.3%,白斑伴有异常增生组织中下降到19.7%,差异有统计学意义(P=0.039)。TβRⅢ弥漫性强阳性细胞数正常组织中为28.0%,白斑不伴异常增生组织中下降到19.1%,白斑伴有异常增生组织中下降到12.6%,差异有统计学意义(P=0.032)。结论 TβRⅡ和TβRⅢ的表达下调在口腔黏膜癌变过程中是一种频发现象,且可以发生在癌变的早期阶段即口腔白斑组织中。     

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。     

整联蛋白连接激酶在口腔白斑及早期浸润癌中的表达

目的 研究整联蛋白连接激酶(integrin-linked kinase,ILK)在口腔自斑及早期浸润癌中的表达特点及演变规律,以期为口腔癌前病变的诊断、治疗及口腔癌的预防提供依据.方法 联合应用免疫组织化学及过碘酸希夫反应(periodic acid Schiff reaction,PAS)方法研究ILK在19例正常口腔黏膜(正常黏膜组)、43例白斑伴上皮单纯增生(单纯增生组)、84例白斑伴上皮异常增生[异常增生组,包括轻、中度异常增生44例(轻中度异常增生组),重度异常增生和原位癌40例(重度异常增牛组)]及54例早期浸润癌(浸润癌组)中的表达情况及分布规律.结果 ILK在正常口腔黏膜中呈阴性表达,在其他3组中的阳性表达率可高达90%(163/181),并且ILK在间质的表达随病变程度的加重而增加(χ2=41.585,P<0.001).白斑从单纯增生至癌变,ILK的表达呈现从上皮浅层向基底层下移的趋势,基底细胞由阴性转为阳性着色,并且伴随从胞质向胞膜的分布改变.重度异常增生组基底层和间质表达之间差异有统计学意义(P=0.029).ILK在早期浸润癌的癌巢表达较癌旁上皮浅,间质阳性的病例[76%(41/54)]较重度异常增生[45%(18/40)]增多.结论 ILK在口腔白斑的癌变中可能起莺要作用,确切机制需进一步研究.     

白斑脱落粘膜上皮细胞与组织上皮细胞微核率相关性分析

目的 检测口腔白班患者脱落粘膜细胞微核细胞率及相应组织细胞微核细胞率,并进行相关性分析,为将该项指标应用于口腔白斑的治疗和判断预后提供依据。方法 采用Ｆｅｕｇｌｅｎ染色方法,对５９例单纯增生、３２例轻和中度异常增生性白斑及２８例重度异常增生性白斑和口腔鳞癌患者的口腔脱落粘膜细胞和组织上皮细胞微核进行了检测,同时检测了１００例健康人的口腔脱落粘膜细胞微核作为正常对照。结果 口腔白斑患者脱落粘膜细胞微     

Immunohistochemical study of syndecan-1 down-regulation and the expression of p53 protein or Ki-67 antigen in oral leukoplakia with or without epithelial dysplasia

BACKGROUND: Leukoplakia is an oral pre-cancerous lesion that sometimes develops into squamous cell carcinoma. Therefore, leukoplakia with epithelial dysplasia is useful for studying carcinogenesis at the cellular level. The purpose of this study was to evaluate a potential association between the loss of syndecan-1 expression and the expression of p53 protein and Ki-67 antigen, and to identify reliable markers for predicting malignant changes in oral leukoplakia with epithelial dysplasia. METHODS: Changes in the expression of syndecan-1, p53, and Ki-67 were examined immunohistochemically in 43 cases of oral leukoplakia with or without epithelial dysplasia. The subjects were categorized as: none, 13 cases; mild dysplasia, 5 cases; moderate dysplasia, 17 cases; and severe dysplasia, 8 cases. The expression of these molecules in normal oral epithelia (22 cases) was also investigated. RESULTS: Strong syndecan-1 expression was observed on the surface of keratinocytes in normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. In normal epithelium, p53 and Ki-67 appeared mainly in the basal cell layer, while they were more widely distributed in leukoplakia. Specifically, significant changes were observed in the labeling index of p53 and Ki-67 in leukoplakia as epithelial dysplasia progressed from mild to moderate or severe. CONCLUSION: Our results reveal that overexpression of p53 protein and Ki-67 antigen, and down-regulation of syndecan-1 expression in the lower part of the epithelium, are associated with dysplastic changes. Therefore, the down-regulation of syndecan-1 expression may be the most important reliable marker for dysplastic changes.     

口腔癌前病变和鳞癌P53表达与微核的关系

目的：分析脱落细胞涂片和组织病理切片检测P53蛋白水平的意义,探讨P53表达与微核的关系,方法：对20例白斑和18例癌患者的口腔粘膜脱落细胞涂片和组织病理切片进行P53表达的免疫组化研究,对脱落细胞涂片还进行计数的分析,结果：组织切片中,P53表达阳性率在上皮异常增生白斑中为60％,在上皮单纯增生白斑中为10％（P＜0．05）,P53蛋白表达阳性组和阴性组织胸微核数无显著性差异。结论：P53蛋白的过表达从肿瘤发生的早期阶段就开始出现,与上皮增生的程度有正相关性,微核计数升高是肿瘤发生中更早期的事件。     

大鼠舌癌变过程中生存素、Bcl-2和p53蛋白的表达

目的 探讨生存素(survivin)蛋白在大鼠舌癌变过程中的表达及其与Bcl-2、p53蛋白表达的相关性.方法 0.002%4-硝基喹啉-1-氧化物(4一nitro-quinoline 1-oxide,4NQO)饮水喂养SD大鼠9～36周建立大鼠舌癌变模型,用免疫组化二步法检测60例大鼠舌癌变过程中生存素、Bcl-2及p53蛋白的表达.结果 36例止常组织中生存素蛋白表达仅1例,而11例异常增生组织中其表达为6例,11例口腔癌组织中其表达为10例.生存素蛋白在正常舌黏膜、异常增生黏膜及舌癌中的阳性表达差异有统计学意义(P<0.001),异常增生及口腔癌组织中生存素蛋白表达显著高于正常黏膜中的表达(P<0.01).在17例生存素蛋白表达阳性的大鼠舌组织中,Bcl-2蛋白阳性表达12例,p53蛋白阳性表达8例;生存素蛋白表达与Bcl-2、053蛋白表达呈正相关(P<0.01).结论 生存素蛋白的表达增高和口腔鳞状上皮的异常增生、癌变有关,提示生存素可能参与了口腔癌的发生、发展;生存素、Bcl-2及p53蛋白的表达可能在口腔癌的发生、发展中起协调作用.     

Follow-up studies in oral leukoplakia.

Follow-up examinations of 670 patients with oral leukoplakia during a 30-year-period showed cancer development in 40 cases, i.e. 6%. Dysplasia was observed in 24% of the histologically examined leukoplakia cases; 13% of the dysplasia cases subsequently showed development of carcinoma. The age distribution revealed the prevalence of leukoplakia in the age-group 51-60 years; that of carcinoma in the age-group of 61-70 years. The sex distribution showed a male-female ratio of 3.2 : 1 in the leukoplakia-group, and a 1.9 : 1 ratio in the carcinoma-group. The tongue and the lips were the site of predilection for malignant transformation and for dysplasia. Among aetiological factors, Candida albicans infection and the simultaneous existence of several aetiological factors seemed to play a role in malignant transformation. Erosive leukoplakia showed the highest risk, developing in 25.9% of the cases into cancer.     

HPV与Survivin在口腔上皮组织中致癌作用研究

目的:研究口腔鳞癌(OSCC)及口腔黏膜白斑(OLK)组织中HPV感染与Survivin的表达,探讨上皮组织肿瘤的形成机制。方法:应用原位杂交法和免疫组化染色法分别检测30例OSCC组织,20例OLK组织及20例正常口腔黏膜组织中HPV及Survivin的表达情况。结果:Survivin在OSCC中的表达高于OLK中的表达,具有统计学意义。HPV阴性的OSCC中Survivin的表达明显高于HPV阳性OSCC组织;HPV阳性的OLK中survivin的表达明显高于HPV阴性的OLK组织。结论:Survivin可能通过抑制细胞凋亡调节HPV对口腔上皮的致癌作用,HPV感染对Survivin的表达水平存在调节作用。     

Scanning electron microscopy of different types of oral leukoplakia: Comparison with normal and malignant oral mucosa

The present study analysed surface architecture of normal, premalignant and malignant oral mucosa using scanning electron microscopy to evaluate its role in early diagnosis of potentially malignant oral lesions. The surface ultrastructure of the buccal mucosa in tobacco chewers showed variations from that of non-chewers. Homogenous leukoplakia demonstrated well-defined intercellular junctions and the microrugal surface pattern as seen in normal mucosa. In verrucous leukoplakia, the surface layer consisted of characteristically-shrunken desquamated hyperkeratotic cells. Erosive leukoplakia had a discontinuous superficial layer along with complete loss of intercellular ridges. Speckled leukoplakia also showed marked abnormalities such as thickened irregular protrusions and evidence of a villuslike pattern. These villus-like structures were comparatively prominent in leukoplakia showing dysplasia. Oral carcinoma showed marked altered surface ultrastructure and had a pattern similar to dysplastic lesions. The irregular swollen elongated protrusions with villous-like structures that were observed in carcinoma and dysplastic lesions can, therefore, be considered as surface markers for potentially malignant leukoplakia.     

抗氧化蛋白Prx1在口腔黏膜白斑中的表达

目的检测抗氧化蛋白Prx1和DNA氧化损伤标记物8-OHdG在口腔黏膜白斑中的表达,探讨Prx1在口腔黏膜白斑中的作用。方法选择40例口腔黏膜白斑,包括单纯增生10例,白斑伴上皮轻度异常增生15例,白斑伴上皮中度异常增生15例,正常口腔黏膜10例。采用免疫组织化学染色方法,分别检测Prx1、8-OHdG在黏膜中的表达。结果口腔黏膜白斑伴上皮中度异常增生组Prx1和8-OHdG染色的MOD值均高于正常组、白斑单纯增生组、白斑伴上皮轻度异常增生组,且差异有统计学意义(P0.01)。结论 Prx1与口腔黏膜白斑的发病有关,口腔黏膜白斑的发生可能与氧化损伤有关。     

Short telomeres in an oral precancerous lesion: Q-FISH analysis of leukoplakia

J Oral Pathol Med (2012) 41 : 372–378 Objectives: A precancerous condition is a lesion that, if left untreated, leads to cancer or can be induced to become malignant. In the oral region, leukoplakia is a lesion that has been regarded as precancerous. In cases of oral carcinoma, we have frequently noticed that a type of leukoplakia histologically demonstrating hyper‐orthokeratosis and mild atypia (ortho‐keratotic dysplasia; OKD) is often associated with carcinoma, either synchronously or metachronously. Therefore, we consider OKD‐type leukoplakia to be a true precancerous lesion. Materials and Methods: In an attempt to clarify the relationship between OKD as a precancerous condition in the oral mucosa and telomere length, we estimated telomere lengths in this type of leukoplakia using quantitative fluorescence in situ hybridization, and also quantified the frequency of anaphase–telophase bridges (ATBs) in comparison with squamous cell carcinoma in situ (CIS) and the background tissues of CIS and OKD. Results: Ortho‐keratotic dysplasia was frequently associated with squamous cell carcinoma (45.0%) and showed significantly shorter telomeres than normal control epithelium, CIS, or the background of CIS or OKD. The frequency of ATBs was much higher in OKD than in control epithelium or CIS. Conclusion: Ortho‐keratotic dysplasia appears to be frequently associated with carcinoma, chromosomal instability, and excessively shortened telomeres, not only in the lesion itself but also in the surrounding background. Therefore, when this type of leukoplakia is recognized in the oral region, strict follow‐up for oral squamous cell carcinoma is necessary, focusing not only on the areas of leukoplakia, but also the surrounding background.