口服白斑患者口腔粘膜脱落细胞微核细胞率的研究

本研究采用Ｆｅｕｇｌｅｎ染色方法，对我院就诊的１２７口服白斑患者和鳞癌患者的口腔脱落粘膜细胞微核细胞进行了检测，同时检测了１００例正常健康人作对照。研究结果表明，口腔白斑患者脱落粘膜细胞微核细胞率明显于正常人，且随着病变程度的加重微核细胞率也增高，各组之间有显著差异，证明该指标可反映口腔白斑的病变程度，可作为癌变早期的观察指标和反映口腔白斑癌变危性大小的标志物。     

口腔白斑患者口腔粘膜脱落细胞微核细胞率的研究

本研究采用Ｆｅｕｇｌｅｎ染色方法，对我院就诊的１２７口腔白斑患者和鳞癌患者的口腔脱落粘膜细胞微核细胞率进行了检测，同时检测了１００例正常健康人作为对照。研究结果表明，口腔白斑患者脱落粘膜细胞微核细胞率明显高于正常人，且随着病变程度的加重微核细胞率也增高，各组之间有显著差异。证明该指标可反映口腔白斑的病变程度，可作为癌变早期的观察指标和反映口腔白斑癌变危险性大小的标志物。     

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。     

口腔粘膜脱落细胞的形态学与微核计数

目的：探讨无创的脱落细胞形态学检查及微核计数的临床意义，评价脱落细胞学在追踪观察白斑及其在癌变早期诊断上的实用价值。方法：对26例白斑和18例鳞癌患者的口腔粘膜脱落细胞涂片：①进行巴氏染色，分析细胞学角化分型、细胞学巴氏分级与病变性质的关系；②计数微核细胞率，分析细胞学巴氏分级与微核计数的联系。结果：上皮单纯增生的白斑均为混合角化，鳞癌多为不全角化。白斑和鳞癌，上皮单纯增生的白斑和鳞癌之间细胞学角化分型有显著性差异（P＜0．001）。上皮异常增生的白斑中，63．64％为巴氏Ⅱ级，而上皮单纯增生的白斑中，6．67％为巴氏Ⅱ级。白斑和鳞癌的细胞学诊断有显著性差异（P＜0．001）。不同巴氏分级的患者，病损处微核细胞率无显著性差异。结论：脱落细胞涂片出现不全角化的病例发生癌变或癌前病变的可能性较。白斑患者脱落细胞涂片中一旦发现细胞学上异形的细胞，就要考虑其组f学上异常增生的可能。微核计数变化的出现早于细胞形态学变化。     

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.     

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。     

CD25~＋ Foxp3~＋调节性T细胞和Th17细胞在口腔白斑组织中的表达

目的：通过观察CD25＋Foxp3＋和IL-17阳性细胞在口腔黏膜白斑（oral leukoplakia,OLK）和口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）组织中的表达情况,探讨Treg细胞和Th17细胞在口腔癌发生发展过程中的变化。方法：采用免疫组织化学方法检测CD25＋Foxp3＋、IL-17阳性细胞在10例单纯增生性白斑、32例异常增生性白斑、13例OSCC和10例正常口腔黏膜中的变化情况。结果：正常口腔黏膜组、单纯增生性白斑组、异常增生性白斑组和OSCC组CD25＋Foxp3＋Treg细胞数量逐渐增高（P〈0.05）,依次为（2.5±0.65）、（5.22±1.19）、（31.4±16.8）和（42.8±12.67）个/每高倍镜视野。重度异常增生白斑组织中,CD25＋Foxp3＋Treg细胞的数量高于轻、中度异常增生白斑组织（P〈0.05）。此外,正常口腔黏膜组、单纯增生性白斑组、异常增生性白斑组和OSCC组中表达IL-17的阳性细胞虽有递增趋势,但差异无统计学意义。CD25＋Foxp3＋Treg细胞和Th17细胞数量改变在口腔白斑和OSCC组织中呈正相关（r=0.318,P〈0.05）。结论：Treg细胞的数量在白斑和OSCC组织中增多,Th17细胞协同Treg细胞,在口腔癌发生发展过程中发挥了一定的作用。     

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。     

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和p53蛋白在口腔白斑和鳞状细胞癌中表达的比较研究

目的比较p16和p53在口腔白斑和口腔鳞状细胞癌中异常表达的情况。方法对17例健康者的口腔粘膜、60例白斑患者和40例口腔鳞状细胞癌患者的病损组织进行了p16和p53蛋白的免疫组化染色。结果正常口腔粘膜、白斑单纯增生、白斑异常增生和口腔鳞状细胞癌的p16阳性率分别为100％、90％、60％和35％，p53蛋白的阳性率分别为12％、27％、50％和73％，p16阳性率和细胞染色强度指数（stainning intensity index，SII）分别与口腔粘膜组织恶性度的增高显著负相关；p53阳性率和S11分别与口腔粘膜组织恶性度的增高显著正相关。p16和p53在不同组织中的阳性率显著负相关；p16和p53在白斑异常增生的协同失活率达23％，在口腔鳞状细胞癌中达到42．5％。p16阳性率、p16SII、p53SII及两种基因均异常的比率在口腔鳞状细胞癌无淋巴结转移和口腔鳞状细胞癌有淋巴结转移患者之间均有显著差异。结论p16可作为早期监视口腔白斑恶变、监测口腔鳞状细胞癌发展进程和判断口腔鳞状细胞癌预后的分子生物学指标。p16和p53失活在白斑癌变和口腔鳞状细胞癌的发展过程中可能有叠加效应。     

Micronucleus—an upcoming marker of genotoxic damage

This study was conceived for the early detection of oral precancer and cancer lesions using a noninvasive reliable technique. Micronucleus assay was performed on oral exfoliated cells of chosen subjects having leukoplakia and squamous cell carcinoma (SCC) using fluorescent (Acridine Orange) and conventional (Feulgen) stainings. The results were analyzed using Mann–Whitney U test, Kruskal–Wallis test, Spearman’s Correlation and SPSS statistical package. The frequency of mean percentage occurrence of micronucleated cells increased significantly in comparison to controls with leukoplakia and squamous cell carcinoma. Subjects with synergism of abnormal oral habits also showed increased micronucleated cells. Fluorescent staining was found to be more sensitive than the conventional one for micronucleus detection. The results clearly demonstrate that micronucleus assay in oral exfoliated cells can be used as a simple reliable marker to assess the genotoxicity and for the early diagnosis of premalignant and malignant lesions. Micronucleus assay is, thus, an easy tool for early detection of cancer.     

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。     

Cytomorphometric analysis of squames obtained from normal oral mucosa and lesions of oral leukoplakia and squamous cell carcinoma

Ramaesh T, Mendis BRRN, Ratnatunga N, Thattil RQ: Cytomorphometric analysis of squames obtained from normal oral mucosa and lesions of oral leukoplakia and squamous cell carcinoma. J Oral Pathol Med 1998; 27: 83–6. © Munksgaard, 1998.
Cell and nuclear diameters (CD and ND) were measured in squames obtained from normal buccal mucosa and lesions of oral leukoplakia and squamous carcinoma (SCC) also from buccal mucosa. The study groups consisted of Group 1: normal buccal mucosa ( n = 40); Group 2: lesions with no epithelial dysplasia ( n = 58); Group 3: lesions with epithelial dysplasia ( n = 27); and Group 4: SCC lesions ( n = 51). The mean CD and ND values were: Group 1: 51.78 (± 0.11) and 8.36 (± 0.49); Group 2: 45.73 (± 0.16) and 8.31(± 0.68); Group 3: 41.32 (± 0.13) and 9.04 (± 0.46); Group 4: 38.58 (± 0.11) and 10.10 (± 0.56) urn, respectively. Correlation between the ND and CD was positive for Group 1 ( r = 0.78, P < 0.05) and Group 2 ( r = 0.33, P < 0.05). There were no significant correlations in Groups 3 and 4. ANOVA showed significant differences ( P < 0.05) for CD between all four groups. Except between Groups 1 and 2, the ND was significantly different ( P < 0.05) between all groups. The results indicate that ND and CD could possibly be sensitive parameters in the diagnosis of oral premalignant and malignant lesions.     

Cellular death but not genetic damage in oral mucosa cells after exposure to digital lateral radiography

The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis, and karyorrhexis) in exfoliated buccal mucosa cells from individuals following digital lateral radiography. A total of 30 healthy patients (15 men and 15 women) indicated to the orthodontic therapy were submitted to digital lateral X-ray. Exfoliated oral mucosa cells were collected immediately before the X-ray exposure and after 10 days. The results pointed out no significant statistically differences (p > 0.05) of micronucleated oral mucosa cells. On the other hand, X-ray was able to increase other nuclear alterations closely related to cytotoxicity such as karyorrhexis, pyknosis, and karyolysis. In summary, these data indicate that exposure to digital lateral radiography may not be a factor that induced chromosomal damage, but it is able to promote cytotoxicity.     

Biomonitoring of oral epithelial cells in smokers and non-smokers submitted to panoramic X-ray: comparison between buccal mucosa and lateral border of the tongue

The aim of the present study was to comparatively evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis, and karyorrhexis) in exfoliated oral mucosa cells from smokers and non-smokers submitted to dental X-ray using two anatomic sites: buccal mucosa and lateral border of the tongue. A total of 15 heavy smokers and 17 non-smokers were submitted to panoramic dental radiography for orthodontic reasons. Individuals had epithelial cells from cheek and lateral border of the tongue mechanically exfoliated, placed in fixative, and dropped in clean slides which were checked for the above nuclear phenotypes. The results pointed out no significant statistically differences (p > 0.05) of micronucleated oral mucosa cells before versus after X-ray exposure for both oral sites evaluated either to smokers or to non-smokers. X-ray exposure was able to increase other nuclear alterations closely related to cytotoxicity such as karrhyorexis, pyknosis, and karyolysis for two groups evaluated. Nevertheless, the most pronunciated effects were found to lateral border of the tongue of smokers. In summary, these data indicate that panoramic X-ray is able to induce cellular death in oral mucosa cells. It seems that lateral border of the tongue is more sensitive site to cytotoxic insult induced by ionizing radiation combined with continuous cigarette smoke exposure.     

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.     

口内超声成像在18例口腔非咀嚼黏膜白斑诊疗中的评价

目的 探讨口腔非咀嚼黏膜白斑的声像图表现,根据声像图特征将黏膜白斑分类,并为临床诊疗方案提供参考依据。方法 选取就诊于上海交通大学医学院附属第九人民医院口腔黏膜科并最终病理确诊为口腔黏膜白斑的患者18例（24处病灶）,病灶分别位于舌部、口底、颊黏膜、唇黏膜。在病灶切取活检前,于超声科行口腔内路径超声检查,观察病灶范围、连续性、有无角化形成、上皮各层厚度及病损处彩色多普勒血流信号。并应用定量分析软件Qontraxt,对白斑区黏膜表面随机取值测量相对回声强度,总结与之对应的病损角化类型。数据应用SPSS 25.0软件包进行统计分析。结果 口腔黏膜白斑声像图表现为出现角化层并增厚,回声增强,中间层表现为低回声增厚条带,部分病灶局部表层回声减低及血流信号增多。白斑区高回声条带明显增厚(P<0.001)、回声增强,其中舌部和颊黏膜差异最显著。低回声条带明显增厚(P<0.001),其中颊黏膜、唇黏膜差异最显著。通过Qontraxt定量分析软件测定表层及角化层回声强度值,判断是否存在角化及角化类型,其中非白斑区为43.28±9.33,白斑正角化为92.88±3.12,白斑不全角化为84.75±5.76。结论 超声成像可以有效观察黏膜白斑并测量上皮内各层厚度,此外可发现特殊伴随改变,如溃疡、感染及癌变等,可为临床诊断、治疗方案制定及治疗后随访提供影像学依据,有助于避免不必要的黏膜医源性损伤或治疗后疾病复发。     

吸烟致口腔癌发生分子机制的研究

目的：研究吸烟对口腔黏膜细胞的遗传毒性，分析与口腔癌发生的关系。方法：采用单细胞凝胶电泳技术，检测24例吸烟者和17例非吸烟者（其中口腔恶性肿瘤12例，良性肿瘤19例，10例健康者）口腔黏膜脱落上皮细胞DNA损伤，按组织病理类型进行分析，观察指标为彗星尾长和彗星率。试验所得数据由SPSS、SAS软件进行统计检验和分析。结果-恶性肿瘤患者的彗星尾长和彗星率均明显高于良性肿瘤患者和健康人，有显著性差异（P〈0．01），良性肿瘤患者与健康者的彗星试验结果无显著差异（P〉0．05），吸烟者的彗星尾长和彗星率均明显高于非吸烟者（P〈0．01）。结论：吸烟可导致口腔黏膜细胞DNA损伤，随肿瘤组织病变程度的加重，DNA损伤程度亦加重。组织细胞DNA损伤与口腔恶性肿瘤的发生密切相关。     

Candida albicans in leukokeratotic lesions of oral mucosa

The potential presence of Candida albicans in oral leukokeratotic lesions, also entailing the need of additional antimiotic therapy, has been quite extensively discussed in literature. Therefore, the aim of this study was to assess the prevalence of Candida albicans isolates in subjects with oral leukoplakia as well as of candidal leukoplakia according to oral mucosa regions. The study included 60 subjects, mean age 46 years. A study group had 28 subjects with oral leukoplakia, whereas a control group comprised subjects free of any pathological alterations of oral mucosa. In all subjects, a clinical oral examination was performed and material for microbiological analysis taken. Following cultivation and incubation, tests of identification and microbiological analysis were carried out on the material thus grown. Results of the study revealed that Candida albicans was present in 67.9% of subjects with oral leukoplakia, which is the highest percentage reported on so far, and in 28.1% of subjects without any pathologic alterations of oral mucosa. The prevalence of candidal leukoplakia was found to be highest in oral mucosa, followed by lips, tongue and sublingual mucosa. Thus, these findings appear to clearly confirm the need of additional use of antimicotics, along with antikeratotic therapy of leukoplakia.     

MAGE-A antigens in lesions of the oral mucosa

Oral squamous cell carcinoma develops continuously out of predamaged oral mucosa. For the physician and pathologist, difficulties arise in distinguishing precancerous from cancerous lesions. MAGE-A antigens are tumor antigens that are found solely in malignant transformed cells. These antigens might be useful in distinguishing precancerous from cancerous lesions. The aim of this study was to verify this assumption by comparing MAGE-A expression in benign, precancerous, and cancerous lesions of the oral mucosa. Retrospectively, biopsies of different oral lesions were randomly selected. The lesions that were included are 64 benign oral lesions (25 traumatic lesions (oral ulcers), 13 dental follicles, and 26 epulis), 26 oral lichen planus, 123 epithelial precursor lesions (32 epithelial hyperplasia found in leukoplakias, 24 epithelial dysplasia found in leukoplakias, 26 erythroplasia with oral epithelial dysplasia, and 41 carcinomas in situ in erythroleukoplakias). The lesions were immunohistochemically stained with the poly-MAGE-A antibody 57B, and the results were compared. Biopsies of oral lichen planus, oral ulcers, dental follicles, epulis, and leukoplakia without dysplasia showed no positive staining for MAGE-A antigens. Leukoplakia with dysplasia, dysplasia, and carcinomata in situ displayed positive staining in 33%, 65%, and 56% of the cases, respectively. MAGE-A antigens were not detectable via immunohistochemistry in benign lesions of the oral mucosa. The staining rate of dysplastic precancerous lesions or malignant lesions ranged from 33% to 65%. The MAGE-A antigens might facilitate better differentiation between precancerous and cancerous lesions of the oral mucosa.