人口腔粘膜白斑p53蛋白、p16蛋白及PCNA的表达及白斑恶变潜能的研究

目的　利用p5 3蛋白、p16蛋白及增殖细胞核抗原 (PCNA)在口腔粘膜白斑 (OralLeukoplakia ,OLK)中的表达 ,评估OLK的恶变潜能。方法　免疫组化技术。结果　正常口腔粘膜p5 3蛋白表达阴性 ,p16、PCNA表达阳性。口腔不典型增生性白斑 (dysplasialeukoplakia ,DLK)p5 3阳性表达率 (5 8 16 % )显著高于单纯增生性白斑 (simplehyperplasialeukoplakia ,SHLK) (12 5 0 % ,P <0 0 5 )。口腔DLK与口腔鳞癌组间p5 3蛋白阳性指数差异有显著性 (P <0 0 5 )。PCNA在口腔DLK中表达分布主要为基底上层模式 ,与正常口腔粘膜及SHLK的基底层分布模式间差异有显著性 (P <0 0 1) ,其PCNA表达阳性指数显著较SHLK为高 (P <0 0 1)。结论　p5 3蛋白表达在OLK由单纯增生向不典型增生转化过程中起主要作用。PCNA阳性指数能较好的反映口腔粘膜病变的增殖水平。PCNA基底上层表达模式能较好反映口腔粘膜白斑的不典型增生。通过对这些基因产物检测 ,可评价OLK的恶变潜能 ,筛选高危白斑 ,为临床治疗提供依据。     

口腔念珠菌白斑中CD44H、CD44v3和CD44v6的异常表达

目的 研究口腔念珠菌白斑（ｏｒａｌ ｃａｍｄｉｄａｌ ｌｅｕｋｏｐｌａｋｉａ,ＯＣＬ）上皮中ＣＤ４４Ｈ、ＣＤ４４ｖ３和ＣＤ４４ｖ６的表达特点及其与炎症、癌变的关系。方法 用免疫组织化学方法对２９例ＯＣＬ上皮中ＣＤ４４Ｈ、ＣＤ４ｖ３和ＣＤ４４ｖ６的强近性表达;重度异常增生上皮人武部出现低表达,与对照组非白念白斑一致;形成微脓肿或炎症密集区的上低表达。结论 口腔念珠菌白斑伴上皮理度异常增生者ＣＤ４４Ｈ     

p53 expression above the basal cell layer in oral mucosa is an early event of malignant transformation and has predictive value for developing oral squamous cell carcinoma

Epithelial dysplasia is usually used to establish the prognosis of oral premalignant lesions. Its assessment, however, is subjective and does not always correctly predict the outcome of the lesions in terms of malignant transformation. Early molecular alteration(s) that dictate the development of cancer should be identified and used to evaluate oral premalignant lesions. In this context, alterations in the expression of p53 were investigated. Thirty-five oral premalignant lesions and 11 carcinomas that developed from them in a period of 16 years were investigated for p53 expression by immunohistochemistry. Normal oral mucosa from healthy individuals and oral benign lesions were used as controls. In benign lesions and normal mucosa, p53 staining, when present, was confined to the basal cell layer. Seven out of 35 (20 per cent) premalignant lesions showed p53 expression clearly above the basal cell layer and six of these (86 per cent) developed carcinomas. Suprabasal p53 expression was found in three lesions with no or mild dysplasia that developed carcinomas. All carcinomas derived from premalignant lesions with p53 suprabasal expression showed p53 expression in neoplastic cells. The combined use of histological parameters (presence of moderate or severe dysplasia) with p53 expression patterns (p53 staining above the basal cell layer) showed the highest sensitivity for the detection of lesions that progressed to carcinoma (91 per cent). When used individually, the p53 expression pattern showed higher specificity than assessment of dysplasia (96 per cent vs. 54 per cent) and higher positive predictive value (86 per cent vs. 44 per cent) for correct prediction of the malignant transformation of the lesions. The results suggest that clear expression of p53 above the basal cell layer is an early event in oral carcinogenesis and an indicator of a developing carcinoma, even preceding morphological tissue alterations. However, since immunohistochemistry cannot always detect changes in p53 expression in lesions preceding carcinoma, p53 immunohistochemical analysis is strongly recommended in conjunction with histological parameters, to increase the sensitivity of detection of cases that will progress to carcinoma. © 1998 John Wiley & Sons, Ltd.     

口腔癌前病变细胞凋亡的原位观察与分析

目的　探讨口腔白斑、扁平苔藓的癌变机制。方法　通过原位末端转移酶标记法 ,观察分析 10例正常口腔黏膜上皮 ,18例扁平苔藓 ,2 3例白斑 ,2 2例鳞癌上皮组织凋亡状况。结果　除单纯上皮增生 ,非糜烂型扁平苔藓外 ,上皮 (轻、中、重 )异常增生 ,鳞癌及糜烂型扁平苔藓的凋亡指数均高于正常 ,差异有显著性。从上皮异常增生到鳞癌凋亡指数逐渐增高 ,糜烂型扁平苔藓的凋亡指数低于鳞癌 ,差异有显著性。结论　细胞凋亡参与白斑癌变的过程 ,在病变不同阶段作用不同。扁平苔藓的发病机制可能与细胞免疫诱导角朊细胞凋亡亢进有关     

部分人群吸烟引起口腔黏膜损害调查研究

目的　了解吸烟与口腔黏膜病变的关系。方法　回顾1998—2 0 0 4年我市部分健康人群体检和来我院口腔科就诊患者的检查资料,对有吸烟史且伴口腔黏膜病变者进行重点分析。结果　受检3335人中有吸烟史者为12 6 0人,占37. 78%。从吸烟者中检查出口腔黏膜有白色损害者6 9人。排除残冠、残根等其他因素,单纯吸烟者黏膜白色损害者有5 7人,占吸烟人数的4 . 5 2 %。结论　吸烟可导致口腔黏膜损害,且与吸烟数量和年限成正比。     

无创检测口腔白斑及鳞癌中人乳头瘤病毒及其分型

[摘要] 目的 探讨口腔白斑（oral leukoplakia,OLK）和口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）中人乳头瘤病毒（human papillomavirus,HPV）及其分型和临床意义。方法 采用无创方法收集30例正常人,103例OLK,30例OSCC的口腔黏膜脱落细胞,采用聚合酶链反应（Polymerase chain reaction,PCR）结合导流杂交技术进行37种HPV基因型别的检测,对受检者进行相关资料分析。结果 正常人检出HPV阳性1例,检出率为3.33%（1/30）,OLK检出HPV阳性5例,检出率为4.85%（5/103）,OSCC检出HPV阳性1例,检出率为3.33%（1/30）,各组间差异无统计学意义（χ2=0.22,P=0.90＞0.05）。其中OLK中有4例为HPV单一型阳性,1例为HPV三重型别阳性。结论 PCR导流杂交检测技术能无创检测口腔HPV分型情况,可应用于临床。HPV在OLK、OSCC中检出率较低,可能与OLK、OSCC的发病关联性不强。     

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Introduction:  We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC.
Methods:  Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive–atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t -test, and logistic regression, respectively.
Results:  We detected HPVs significantly more frequently in lesions than in controls ( P  ≤ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL.
Conclusion:  HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.     

Increased expression of TRPV1 in squamous cell carcinoma of the human tongue

Objectives:  Recent reports have unambiguously identified the presence and the growth-modulatory role of transient receptor potential vanilloid-1 (TRPV1), a central integrator of pain sensation, on numerous non-neuronal cell types and, of great importance, in certain malignancies. In this study, we have investigated the molecular expression of TRPV1 in the human tongue and its high-incidence malignant (squamous cell carcinoma, SCC) and premalignant (leukoplakia) conditions.
Methods:  Immunohistochemistry, Western blotting and quantitative 'real-time' Q-PCR were performed to define the expression of TRPV1.
Results:  A weak and sparse TRPV1-specific immunoreactivity was identified in the basal layers of the healthy human tongue epithelium. By contrast, we observed a dramatically elevated TRPV1-immunoreactivity in all layers of the epithelium both in precancerous and malignant samples. Furthermore, statistical analysis revealed that the marked overexpression of TRPV1 found in all grades of SCC showed no correlation with the degree of malignancy of the tumours. Finally, the molecular expression of TRPV1 was also identified in an SCC-derived cell line and was shown to be increased in parallel with the accelerated growth of the cells.
Conclusion:  Collectively, our findings identify TRPV1 as a novel, promising target molecule in the supportive treatment and diagnosis of human tongue SCC.     

Anatomic Site Based Ploidy Analysis of Oral Premalignant Lesions

The location of oral leukoplakia correlates strongly with the probability of finding dysplastic or malignant alterations at biopsy. It is well established that early detection can dramatically improve the 5-year survival rates for oral squamous cell carcinomas. Since aneuploidy is predictive of future conversion to malignancy, we hypothesized that dysplastic lesions from high-risk sites (floor of mouth, tongue and lips) would exhibit greater aneuploidy than low-risk sites (palate, gingiva and buccal mucosa). Epithelial sections from 60 archival samples diagnosed as mild dysplasia (36 females, 20 males) from various high/low risk locations were stained with Blue Feulgen Stain for DNA Ploidy Analysis (Clarient, Aliso Viejo, CA) and ploidy was analyzed using a ChromaVision ACIS II (Clarient, ALiso Viejo, CA) Image cytometry system. A DNA histogram was generated using an image analyzing software that evaluated the amount of Feulgen stain which is proportional to the amount of nuclear DNA. An ANOVA analysis followed by the Student’s‘t’ test revealed significant differences between means (P ≤ 0.05). Lesions originating from lateral/ventral tongue (85%), floor of mouth (50%) and soft palate (44%) exhibited a higher frequency of aneuploidy than lesions from gingiva (22%) and lower lip (25%). This pilot study demonstrates that dysplastic lesions from high-risk sites such as the floor of the mouth and lateral/ventral tongue have higher frequency of aneuploidy.