Survivin在口腔扁平苔藓癌变过程中的表达

目的 探讨凋亡抑制因子Survivin在口腔扁平苔藓(OLP)、口腔鳞状细胞癌(OSCC)中的表达及意义。方法采用免疫组织化学SP法检测40例糜烂型OLP组织、40例OSCC组织以及26例正常口腔黏膜组织中Survivin蛋白的表达,并分析其意义。结果Survivin蛋白在正常口腔黏膜、糜烂型OLP及OSCC中的表达率...     

HERG1在口腔扁平苔藓和口腔鳞状细胞癌中的表达

目的：研究钾离子通道蛋白HERG1在正常口腔黏膜（normal oral mucosa,NOM）、口腔扁平苔藓（oral lichen planus,OLP）、口腔鳞状细胞癌（squamous cell carcinoma,OSCC）中的表达及意义。方法：免疫组织化学技术检测16例NOM、20例OLP、30例OSCC组织中HERG1的表达。采用χ2检验,P〈0.05为差异具有统计学意义。结果：HERG1在OSCC中的表达强度高于OLP（P〈0.05）,HERG1在OLP组织的表达高于正常组织（P〈0.05）,且糜烂型OLP中的表达高于非糜烂型OLP（P〈0.05）,差异均具有统计学意义。结论：HERG1可能与OLP及OSCC的发生发展有一定的关系。     

K_v3.4在口腔扁平苔藓和口腔鳞状细胞癌中的表达

目的:研究钾离子通道蛋白kv3.4在正常口腔黏膜(normal oral mucosa,NOM)、口腔扁平苔藓(oral lichen planus,OLP)、口腔鳞状细胞癌(squamous cell carcinoma,OSCC)中的表达及意义。方法:免疫组织化学技术检测16例NOM、20例OLP和30例OSCC组织中kv3.4的表达,采用Wilcoxon秩和检验,α=0.05。结果:kv3.4在OSCC中的表达强度高于OLP(P<0.05),kv3.4在OLP组织的表达高于正常组织(P<0.05),且糜烂型OLP中的表达高于非糜烂型OLP(P<0.05),差异均具有统计学意义。结论:kv3.4可能与OLP及OSCC的发生、发展有一定的关系。     

iNOS在口腔扁平苔藓癌变过程中的表达研究

目的 :研究诱导型一氧化氮合酶 (iNOS)在口腔扁平苔藓、口腔鳞状细胞癌发展过程中的表达水平及其作用。方法 :以正常口腔黏膜作对照 ,采用免疫组化SP法检测 2 5例口腔扁平苔藓和 10例口腔鳞状细胞癌组织中的iNOS表达。结果 :正常口腔黏膜iNOS阴性表达 ;扁平苔藓组和鳞癌组iNOS表达较正常黏膜组均非常显著增加 (P <0 .0 1) ;扁平苔藓组与鳞癌组之间以及扁平苔藓组内部按上皮异常增生程度分组之间iNOS的表达均无显著差异 (P >0 .0 5 )。结论 :iNOS在口腔扁平苔藓伴上皮异常增生和鳞癌中高表达 ,在口腔鳞癌的发生发展中起着重要的作用。     

表皮生长因子受体在口腔扁平苔藓、口腔乳头瘤及口腔鳞状细胞癌中的表达

目的:研究表皮生长因子受体(epidermal growth factor receptor,EGFR)在口腔扁平苔藓(OLP)、口腔鳞状细胞乳头瘤(SCP)及口腔鳞状细胞癌(SCC)中的表达,探讨其在口腔黏膜炎症、增生及癌发生过程中的意义.方法:用免疫组化方法检测EGFR在20例口腔黏膜扁平苔藓(单纯增生10例,伴糜烂10例)、20例口腔乳头瘤、20例口腔鳞状细胞癌及5例正常口腔黏膜中的表达.采用Fromowitz法计数阳性细胞.应用SPSS11.5软件包分析EGFR在不同病变中的表达差异.结果:EGFR在非糜烂型扁平苔藓组主要表现为弱阳性表达;糜烂型扁平苔藓组强阳性表达率为20％;乳头瘤组的强阳性表达率为25％;鳞状细胞癌的强阳性表达率为60％.扁平苔藓糜烂组和非糜烂组之间EGFR强阳性表达率有显著差异(P＜0.05);糜烂组OLP与乳头瘤组的强阳性表达率无显著差异;口腔鳞癌组的强阳性表达率显著高于扁平苔藓组及乳头瘤组.结论:EGFR可能成为口腔鳞癌化学预防作用的重要靶点.     

COX-2在口腔扁平苔藓、口腔乳头状瘤及口腔鳞状细胞癌中的表达

目的:研究COX-2在口腔扁平苔藓(OLP)、口腔乳头状瘤(SCP)及口腔鳞状细胞癌(SCC)中的表达情况,探讨其在口腔黏膜炎症、增生及癌发生过程中的意义。方法:用免疫组化方法检测COX-2在20例口腔黏膜扁平苔藓(单纯增生10例,伴糜烂10例)、20例口腔乳头状瘤(单纯增生10例,伴糜烂10例)、20例口腔鳞状细胞癌及5例正常口腔黏膜中的表达情况。采用Fromowitz法计数阳性细胞。应用统计学方法分析COX-2在不同病变中的表达。结果:在舌背斑块型扁平苔藓中为阴性或弱阳性表达;在糜烂型扁平苔藓中50%为中度阳性表达,40%为强阳性表达。在口腔乳头状瘤中,同样发现单纯增生的乳头状瘤组织中COX-2的表达为阴性或弱阳性,合并炎症的乳头状瘤组织中均有COX-2的高表达。本实验结果显示,糜烂型扁平苔藓组及乳头状瘤组与鳞癌组相比较,COX-2的强阳性表达无率明显差异。但COX-2在口腔鳞癌中的表达细胞与糜烂型扁平苔藓组及乳头状瘤组有明显差异。结论:扁平苔藓组和乳头瘤组炎症程度与COX-2的高表达有一定的相关性。即随着炎症加重,COX-2的表达加强。口腔鳞癌中炎症程度与COX-2的高表达无一定的相关性。     

FOXP3和GITR在口腔扁平苔藓及口腔鳞状细胞癌中的表达及意义

目的研究FOXP3、GITR在口腔扁平苔藓（OLP）和口腔鳞状细胞癌（OSCC）组织中的表达及其意义。方法采用免疫组化方法检测30例OLP组织、30例OSCC组织和15例口腔正常黏膜（NOM）组织中FOXP3、GITR的表达。结果NOM组FOXP3和GITR阴性表达;OLP组和OSCC组FOXP3和GITR表达分别较NOM组显著增加（P〈0.01）;OLP组和OSCC组之间FOXP3和GITR表达无显著性差异（P〉0.05）;FOXP3和GITR在OLP组和OSCC组中的表达存在正相关关系。结论在OLP的发生及发展成OSCC过程中,FOXP3和GITR均可能起着一定的作用。     

舌鳞状细胞癌中p73、p63和p53基因的表达

目的：研究p73、p63和p53基因蛋白在舌鳞状细胞癌中的表达及其意义。方法：用免疫组织化学S－P法检测64例舌鳞状细胞癌组织标本p73、p63和p53基因蛋白表达。结果：舌鳞癌中p73、p63和p53基因蛋白阳性率分别为61％、92％和50％。p73蛋白表达与T分类(r=0.344,P=0.057)、区域淋巴结转移（r=0.334,p=0.007)、肿瘤侵袭方式（r=0.340,P=0.060)和不良预后（r=-0.473,P=0.000)相关。p63与所有临床病理特征和预后无关。p53与区域淋巴结转移（r=0.263,P=0.036)和不良预后（r=-0.342,P=0.013)相关。结论：p73和p53表达有助于判断舌鳞癌的生物学行为和预后。p63可能是鳞状上皮源性肿瘤的标记物。     

p73在口腔黏膜白斑和口腔鳞癌中的表达

目的：观察p73在口腔黏膜白斑和口腔鳞癌中的表达,了解p73在口腔鳞癌发生过程中的变化规律。方法：白斑病理标本20例,口腔鳞状细胞癌病理标本31例,另取正常口腔黏膜10例,采用免疫组化检测方法观察p73的表达。应用SPSS11.0软件包对实验结果进行χ^2检验和单因素方差分析。结果：口腔白斑和口腔鳞癌病变组织中p73的表达率分别为65%和90.3%,均显著高于正常黏膜组（20%）,且随组织恶性程度增高呈明显上升趋势,正常黏膜上皮组、白斑组与鳞状细胞癌3组间比较,差异有统计学意义（P〈0.05）。结论：p73的表达与口腔鳞癌的癌变过程密切相关,可作为口腔白斑癌变的标志物。     

Detection of antibodies against p63 and p73 isoforms in sera from patients diagnosed with oral lichen planus

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease of oral mucosa. Despite numerous publications and intense research, the etiology of OLP is still unknown, however, autoimmunity as a possible causative factor has been discussed. METHODS: In the present study sera from 20 patients clinically and histologically diagnosed with OLP were analyzed for antibodies directed toward p53, p63, and p73 using Western blot. RESULTS: Sera from two patients reacted with all six p63 isoforms, and one also with p73. The strongest reaction was noted against the TAp63beta protein, which is the most potent transactivator of all p63 proteins and is implicated in the differentiation of stratified epithelia. CONCLUSIONS: This is the first demonstration of antibodies directed against all p63 and some p73 isoforms in sera from patients diagnosed with OLP.     

Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation

BACKGROUND: Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p63 gene encodes six different proteins and is expressed at high levels in SCCHN. METHODS: Biopsies from patients diagnosed with OLP and GVHD were analysed for p63 protein expression using antibodies distinguishing between the major isoforms expressed in normal epithelia, in parallel with biopsies from normal buccal mucosa and SCCHN. RESULTS: In OLP and GVHD a decreased expression of all p63 isoforms was seen, while expression of p53 protein was upregulated, compared with normal mucosa. In SCCHN, p63 was abundantly expressed and some tumours showed strong p53 staining, suggestive of p53 mutation. CONCLUSIONS: Decreased p63 and increased p53 expression in OLP and GVHD indicates a coordinated action of these two related proteins to protect the oral mucosae from the damaging effects of underlying inflammation. In SCCHN disruption of the TP53 gene and overrepresentation of certain p63 isoforms has been seen, indicating that this could lead to neoplastic transformation.     

The use of a novel ELISA method for detection of antibodies against p63 in sera from patients diagnosed with oral and/or genital and skin lichen planus

J Oral Pathol Med (2010) 39 : 486–490 Lichen planus is a chronic inflammatory disease of mucosa and skin affecting approximately 1–2% of the adult population. Autoimmunity has been implicated in the etiology of this disease, and recently we detected antibodies directed against all six p63 isoforms in sera from 2 out of 20 patients diagnosed with oral lichen planus (OLP) using Western blot analysis. Here we have developed an ELISA method for screening sera for presence of autoantibodies directed against p63. Using the same sera as previously analysed, we show that the optical density ratios for sera from the two patients with known autoantibodies was considerably higher compared to mean optical density ratios for all samples as well as controls analysed. Applying this novel ELISA technique for screening of sera from an additional group of 46 patients with oral and/or genital or skin lichen and 43 matched controls, we detected another three patients with autoantibodies against the p63 proteins. These data are discussed together with the observation that all five patients with detectable p63 autoantibodies from our two studies had clinically severe disease symptoms.     

口腔扁平苔藓组织中p73和p14^ARF基因表达与癌变的关系

目的探讨p73、p14^ARF在口腔扁平苔藓组织中的表达与癌变的关系。方法采用免疫组化方法,分别检测口腔扁平苔藓、口腔鳞状细胞癌和正常口腔粘膜各30例组织中p73、p14^ARF的表达情况;采用美国Media Cybernetics公司的Image Plus5.0专业图像分析软件进行IOD值（累计光密度值）的测量。结果p73表达的IOD值在正常口腔粘膜、口腔扁平苔藓及口腔鳞状细胞癌中不断增高,而p14ARF表达的IOD值在正常口腔粘膜、口腔扁平苔藓及口腔鳞状细胞癌中却逐渐下降。两组间有统计学意义（P〈0.05）。p73、p14^ARF在口腔扁平苔藓、正常口腔粘膜、口腔鳞状细胞癌组织中的表达呈负性相关性（P〈0.05）。结论p73、p14^ARF这两个基因在OLP的癌变过程中具有一定的作用。     

Prognostic value of cyclin D1, p27, and p63 in oral leukoplakia

BACKGROUND: Studies on the expression of genes regulating cell proliferation and apoptosis are essential to help better understand the severity and possible malignant transformation of oral leukoplakia. METHODS: The characteristics of cyclin D1, p27, and p63 were investigated in this microscopic study, complementing our previous results with Ki67, p53, and the apoptosis index. Clinical and histologic as well as immunohistochemical studies were carried out on oral leukoplakia of 18 patients. Homogenous, or non-homogenous (nodular or speckled) and erythroleukoplakia were determined clinically. Pathologic classification was performed according to the degree of dysplasia. Immunoperoxidase reaction for cyclin D1, p27, and p63 was carried out on the biopsy specimens and the positivity of the reactions was calculated for 1000 epithelial cells. RESULTS: The expression of cyclin D1 increased in parallel with the severity of leukoplakia. The p27 index was 14-16% in homogenous and nodular leukoplakias but it was substantially lower to 1-2% in erythroleukoplakia. The p63 index was 10% in homogenous, 5% in nodular or speckled, but nearly 20% in erythroleukoplakia, on the average. CONCLUSION: These results suggest that the characteristic expression of cyclin D1, p27, and p63 in various forms of leukoplakia may be of prognostic value.     

Prognostic impact of p53 and p63 immunoexpression in oral squamous cell carcinoma

BACKGROUND: The role of p53 and p63 proteins in the prognosis of oral squamous cell carcinoma (OSCC) is still debatable. Our aim here was to investigate the relationship between the immunoexpression of these proteins with some clinicopathologic parameters of prognostic significance in OSCC. METHODS: Formalin-fixed paraffin-embedded sections from 106 patients were used for study together with the following data: primary site, histologic differentiation, recurrences, metastasis, disease-free survival and overall survival (OS). RESULTS: In OSCCs, the positive rate for p63 protein immunoexpression (87.8%) was higher than p53 (52.8%). p53 expression correlated with metastasis. Tumors negative for p53 and with strong intensity for p63 expression had a significantly higher OS. CONCLUSIONS: p53 overexpression is associated with a larger number of metastases and is correlated with a poor outcome as well as decreased intensity in p63 immunoexpression.     

Expression of p63 and CD44 in oral squamous cell carcinoma and correlation with clinicopathological parameters

Squamous cell carcinoma (SCC) is the sixth most frequent malignant tumor of the head and neck region. Despite advances in therapeutic options over the last decades, the rate of mortality and morbidity has not been improved markedly. A small subset of cells, cancer stem cells (CSCs), with self-renewal properties have become a major focus of current cancer research. CD44 and p63 are identified as candidate stem cell markers in normal squamous epithelium and SCC. The role of these markers in oral squamous cell carcinoma (OSCC) is still debatable. The aim of this study was to evaluate immunohistochemical expression of these markers in OSCC samples and also correlates the expression of these markers with some clinicopathological parameters of prognostic significance including histological grading, TNM staging, overall survival (OS) rate as well as patients’ age, gender, and tumor location. CD44 and p63 were expressed in all studied lesions with different degrees. Statistically significant difference was observed between CD44 and p63 expression with tumor grade and stage with higher expression in high grade and advanced OSCCs. No significant relationship was detected between markers immunoreactivity and patients age, gender, tumor location as well as OS. These markers can possibly advance our understanding of the initiating mechanisms and pathogenesis of OSCC and also result in novel therapeutic target in cancer treatment.