云芝精华（PSP）防治口腔白斑癌变的临床研究

目的 探寻能阻断或逆转口腔上皮异常增生的中草药,评价PSP对白斑癌变的防治效果。方法 对有上皮异常增生的口腔白斑患者连续给PSP口服3月,观察其治疗前后的临床症状,并作病理切片分析。结果 充血糜烂症状见有明显改善,约40%患者的疼痛,牵拉、粗糙感有不同程度好转,约60%患者的上皮异常增生程度得到减轻。结论 PSP对口腔白斑有阻断癌变的临床疗效。     

EMS1基因扩增与口腔黏膜癌变的相关研究

目的 了解EMS1基因扩增是否参与口腔黏膜癌变。方法采用显微解剖技术分别获取正常口腔黏膜上皮，口腔白斑患者的单纯增生，轻、中、重度异常增生上皮和原发性口腔鳞癌组织标本78例，应用差示PCR反应检测EMS1基因扩增。结果①分别有20．0％的口腔白斑组织，57．6％的口腔鳞癌组织观察到EMS1扩增；②在口腔黏膜癌变进程中，EMS1扩增开始于中度异常增生黏膜，在伴有淋巴结转移的口腔鳞癌组织中其扩增率有显著增高(P=0．015)。结论EMS1基因扩增与口腔黏膜癌变的演进相平行，似是口腔黏膜癌变的早期分子事件。     

白斑癌变危险因素与口腔白斑病分期体系的关系

目的：通过对209例口腔白斑患者癌变危险因素与LSCP分期分级关系的综合分析，探讨LSCP分期分级方法的临床意义。方法：首先进行单因素卡方检验，观察性别、病史、吸烟、饮酒，病损数、部位、大小、临床类型及病理分型与LSCP分期体系的关系。筛选对LSCP分期有意义的变量选入多元Logistic回归分析模型。其次对这些因素在LSCP分期中患Ⅳ期白斑相对于Ⅰ、Ⅱ、Ⅲ期白斑的危险性进行分析，并观察各因素对LSCP分期分级的影响。结果：性别、部位、损害类型及病理分型被选入多元Logistic回归分析模型。多元Logistic回归分析表明，女性患者白斑的危险性是男性的2．49倍，舌部及口底白斑危险性高于其他部位，疣 状白斑的危险性是均质型白斑的10．00倍，中度异常增生白斑的危险性是单纯增生或轻度异常增生性白斑的276．48倍，重度异常增生是单纯增生或轻度异常增生性白斑的499．55倍。重度异常增生白斑对LSCP分期的贡献最大。结论：LSCP分期体系可以全面描述白斑的499．55倍，重度异常增生白斑对LSCP分期的贡献最大。结论：LSCP分期体系可以全面描述口腔白斑的特点，有助于对病损癌变危险性综合评估，可以指导临床追踪观察和协助选择最佳治疗方案。     

口腔黏膜白斑与念珠菌感染的临床分析

目的：研究口腔白斑念珠菌感染的临床和病理学特征。方法：利用过碘酸雪夫染色诊断念珠菌感染,回顾性分析448例白斑患者的活检组织中念珠菌感染率,并分析年龄、性别、白斑病损部位、白斑上皮异常增生等因素与感染的关系。结果：白斑组织中念珠菌的感染率14．1％。念珠菌性白斑比普通型白斑的上皮异常增生发生率更高（57．1％vs．33．8％）。回归分析显示＞60岁的老年患者、舌部白斑和上皮异常增生是念珠菌易感因素。结论：念珠菌感染和上皮异常增生密切相关。伴有上皮异常增生的舌部白斑的老年患者更易感染念珠菌。     

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。     

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。     

癌前病变口腔上皮中细胞粘附分子CD44v3和CD44v6表达的改变

目的　研究细胞粘附分子CD44v3和CD44v6在口腔癌前病变中的表达特点及其与癌变的关系。方法　用SP免疫组织化学染色法检查 85例正常、单纯及异常增生的口腔上皮和口腔鳞癌中CD44v3和CD44v6的表达。结果　正常及单纯增生口腔上皮细胞膜有CD44v3和v6的强表达 ,上皮染成网状。上皮轻度异常增生变化不明显。随上皮异常增生程度加重 ,上皮深层细胞出现CD44v3和v6低表达 ,染色变浅或无染色 ,12例重度异常增生者均出现低表达。同一标本中既有上皮单纯增生又有上皮中、重度异常增生的 9例中 ,8例有CD44v3和v6的低表达。鳞状细胞癌的浸润缘有上述低表达 ,部分转移灶较原发灶染色浅。结论　上皮中、重度异常增生时 ,CD44v3和v6表达下降。这种低表达可能与异常增生时细胞粘附力下降及癌变时发生基底膜浸润有关。     

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。     

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,p53,Ki67在口腔癌前病变表达及4年临床随访

目的 :研究 p16,p5 3 ,Ki-67蛋白表达与口腔癌前病变的关系。 方法 :采用免疫组织化学LsAB法对43例上皮异常增生 ( 2 0例轻度上皮异常增生 ,2 3例重度上皮异常增生 )和 2 0例正常口腔黏膜 p16,P5 3和Ki -67蛋白的表达进行研究 ,并对上皮异常增生患者实际癌变率做了 4年追踪。结果 :正常黏膜组 ,p5 3不表达 ,Ki -67少量表达 ,p16的阳性表达为 10 0 %。轻度上皮异常增生 ,p5 3 ,Ki-67少数表达 ,p16表达率为 86.96%。重度上皮异常增生 ,p5 3和Ki-67过度表达 ,p16表达明显下降 ,与正常黏膜 ,轻度上皮异常增生相比差异显著 (P <0 .0 5 )。p5 3和Ki-67蛋白过度表达而 p16呈低表达与实际口腔癌前病变癌变率有一定相关性。 结论 :口腔黏膜癌变是一个由量变到质变的过程 ,它们的调控基因 p16,p5 3 ,Ki -6发生了显著的变化 ,可能起着重要的调控作用。     

口腔黏膜白斑癌变的相关危险因素分析

目的 通过对409例口腔黏膜白斑患者的回顾性综合分析,探讨口腔黏膜白斑癌变的相关危险因素.方法 首先进行单因素检验,观察性别、年龄、病程、系统疾病、吸烟、饮酒、病变部位、临床类型、病变数量、病变范围、症状与口腔黏膜白斑组织病理的关系,筛选与口腔黏膜白斑组织病理相关的变量,进入多元Logistic回归分析模型,计算这些因素的相对危险度(OR值)及95%可信区间.结果 409例口腔黏膜白斑中52例(包括9例重度异常增生)发生了癌变,癌变率为12.7%.其中,性别、年龄、临床分型、病变部位和症状被选入多元Logistic回归分析模型.多元Logistic回归分析结果表明:与单纯增生相比,发生轻中度异常增生的危险性,女性口腔黏膜白斑患者是男性的2.40倍,颗粒型口腔黏膜白斑是均质型的2.81倍,危险区是非危险区的1.98倍,伴有症状的口腔黏膜白斑是无症状的1.84倍.发生重度异常增生及癌变的危险性,女性患者是男性患者的3.11倍,颗粒型、溃疡型、疣状型口腔黏膜白斑分别是均质型的4.50、5.63、4.09倍,危险区是非危险区的2.79倍,伴有症状的口腔黏膜白斑是无症状的4.38倍.结论 口腔黏膜白斑癌变与性别、年龄、临床类型、病变部位及症状等相关.     

Immunohistochemical analysis of the p53 tumor suppressor gene product in oral leukoplakia

Squamous Cell Carcinoma (SCC) is the most frequent malignancy in the oral cavity. p53 protein has been reported to be expressed at high levels in malignant lesions, while the level in premalignant lesions has yet to be determined. In this study, oral leukoplakia and oral SCC were examined. Seventy-four incision or excision samples from 43 cases diagnosed as leukoplakia, and 41 samples from 37 SCC cases in the oral cavity, were obtained. All samples (formalin-fixed, paraffin embedded) were examined immunohistochemically for overexpression of p53 protein with monoclonal antibody BP 53-12. As the result, 1. Twenty-two out of 43 leukoplakia cases, and 29 out of 37 oral SCC cases, were positive for p53 protein. 2. p53 protein was overexpressed in premalignant lesions, especially in the cases with moderate and severe epithelial dysplasia. 3. There was a relation between p53 protein expression and pathological features of leukoplakia (epithelial dysplasia), statistically. 4. There was a relation between p53 protein expression and clinical features of leukoplakia, statistically. 5. Malignant transformation during clinical observation was seen in 11 cases. Nine out of 11 cases were positive for p53 even before malignant transformation. Since in cancer-development cases, p53 staining was detected even before malignant transformation of oral leukoplakia to squamous cell carcinoma, it is indicated that p53 accumulation occurred at a early stage of cancer-development. In conclusion, immunohistochemical analysis of p53 protein is suggested to be useful diagnostic procedure for oral leukoplakia, which may develop into oral SCC.     

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.     

Malignant transformation of oral verrucous leukoplakia: a clinicopathologic study of 53 cases

J Oral Pathol Med (2011) 40 : 312–316 Background: Oral verrucous leukoplakia (VL) is one of the non‐homogenous oral leukoplakias. The objective of this study was to investigate the clinicopathologic features of VL and identify the clinicopathologic risk factors that might be associated with VL malignant transformation from China. Methods: Among 1541 patients with oral leukoplakia, a total of 53 patients with clinical and histopathologic diagnosis of VL between 1996 and 2009 were reviewed retrospectively in our hospital. Results: Of the 53 patients, 11 (20.8%) with VL were observed to develop cancer in the study period. The average age at diagnosis was 59.8 years with a male/female ratio of 1.7:1. Tongue was the predominant site (41.5%). Multivariate regression analysis revealed that the elderly patients (>65 years old) were associated with 8.36‐fold [95% confidence interval (95% CI), 1.45–48.09; P = 0.017] increased risk of malignant transformation compared with the non‐elderly patients. The lesion located on gingiva was associated with 20.81‐fold (95% CI, 1.94–222.80; P = 0.012) increased risk of malignant transformation compared with tongue. However, the gender, smoking, alcohol intake, and epithelial dysplasia were not risk factors. Conclusion: Clinicopathologic features of VL in China were elucidated. The utilization of age and lesion site at diagnosis as significant factors for evaluating malignant transformation risk in patients with VL was suggested. Further studies are required to investigate the roles of the potential risk factors in the VL malignant transformation.     

Development of squamous cell carcinoma from pre-existent oral leukoplakia: with respect to treatment modality

The present study was undertaken in order to determine whether surgical treatment of oral leukoplakia reduces the risk of the subsequent development of carcinoma. This study included 142 patients with oral leukoplakia who received or did not receive surgical treatment. All subjects were followed-up for more than 6 months with a mean follow-up period of 4 years. Malignant transformation rate was lower among patients who received surgical excision (1/75) than among those who did not receive surgical treatments (4/51). However, the malignant transformation rates were high in patients who received cryosurgery (3/12) or cryosurgery plus surgical excision (1/4). There was no obvious relation between the grade of epithelial dysplasia and the rate of malignant transformation. Our results suggest that surgical excision of oral leukoplakia may reduce the risk of the subsequent development of carcinoma.     

Potentially malignant epithelial oral lesions: discrepancies between clinical and histological diagnosis

OBJECTIVE: To evaluate the discrepancy index between the clinical and histological diagnosis and the prevalence of epithelial dysplasia and carcinoma in 45 patients with potentially malignant epithelial oral lesions (PMEL).PATIENTS AND METHODS: We submitted 45 patients with PMEL to clinical examination and obtained a biopsy from each. The results of histological diagnosis were compared to the clinical diagnosis.
RESULTS: Clinical diagnosis showed that the most common PMEL was leukoplakia followed by lichen planus and by actinic cheilitis associated with leukoplakia. The most common site was the buccal mucosa. Histological diagnosis revealed that 46.7% of the PMEL were lichen planus. The discrepancy index between clinical and histological diagnosis was 24.4%. The higher discrepancy index occurred among leukoplakias. The prevalence of epithelial dysplasia and carcinoma was 17.8%.
CONCLUSIONS: We conclude that all PMEL should be submitted to a microscopic analysis because the discrepancy between clinical and histological diagnosis was present in a quarter of these lesionS. Otherwise, the epithelial dysplasia and carcinoma were more frequent in the leukoplakias.     

Recurrence patterns of oral leukoplakia after curative surgical resection: important factors that predict the risk of recurrence and malignancy

J Oral Pathol Med (2012) 41 : 682–688 Background: Oral leukoplakia can be treated using a variety of treatment procedures; however, the lesions recur in many cases irrespective of the treatment procedure used. The rate of recurrence was from 7.7% to 38.1%. This study aims to identify the important factors that can lower the risk of recurrence of oral leukoplakia treated by curative surgical resection. Methods: The clinical records of 52 patients with oral leukoplakia (53 lesions) who underwent curative surgical resection between 2004 and 2009 were retrospectively analyzed for the rate of recurrence, clinical outcome, epithelial dysplasia, lesion location, and resection margins. Results: The recurrence rate following curative surgical resection was 15.1%, with the most common site being the gingiva. Malignant transformation occurred in a single patient (1.9%). Minimal resection margins (<3 mm) were observed in many patients with recurrent disease, and recurrence was more likely in cases with positive margins (epithelial abnormalities at the resection margins) than in those with negative margins. There was no significant association between recurrence and the degree of epithelial dysplasia. Conclusions: Our data suggest that surgical resection of oral leukoplakia is curative only if all areas of epithelial abnormalities are identified and resected. Moreover, an adequate resection margin may reduce the risk of recurrence.     

Premalignant oral mucosal diseases

A premalignant phase in the development of oral cancer is predicted by the classic model of experimental epithelial carcinogenesis. Virtually all oral squamous cell carcinomas arise from a premalignant precursor, but it is difficult to specifically define the term premalignant. Oral pathologists use the term epithelial dysplasia to indicate microscopic features in a biopsy specimen that are associated with a risk of malignant change and then assign a grade of severity. There is good correlation between higher grades of dysplasia and increasing risk of cancer but less so with the lower grades. The clinical appearances manifested by oral epithelial dysplasia and early oral cancer include leukoplakia, erythroplakia, and speckled leukoplakia. This paper discusses and illustrates these clinical lesions, their associated risk factors, their relationship to epithelial dysplasia, and the associated risk of evolution into oral cancer.     

Oral exfoliative cytology of smokers at discrete clinical stages using AgNOR staining.

OBJECTIVE: This study was designed to evaluate oral exfoliative cytology of smokers without any clinically evident lesion and smokers with leukoplakia or oral cancer using AgNOR staining. STUDY DESIGN: Cytological smears of 30 smokers without lesion, 30 smokers with leukoplakia, 30 smokers with oral cancer and 30 non-smokers (control group) were studied using one step silver staining method. The AgNOR count was established on 100 cells. Mean AgNOR count and mean % of cells with 5 or more AgNORs was evaluated. The count values of groups were compared and analysed using Student's unpaired t-test. RESULTS: The mean AgNOR count for control group was 2.94 +/- 0.325, smokers without lesion 3.79 +/- 0.480 smokers with leukoplakia 3.89 +/- 0.433 and oral cancer 4.96 +/- 0.467. Mean % of cells with 5 or more AgNORs was 11.7, 26.5, 30.2 and 55.8 for control group, smokers without lesion, smokers with leukoplakia and oral cancer respectively. CONCLUSION: Analysis of AgNORs suggest that smoking influences proliferative activity in cells of smokers without any clinical lesion and that oral cancer shows highest proliferative activity.     

Effective management of smoking in an oral dysplasia clinic in London

BACKGROUND: Precancerous lesions precede the development of oral cancer; of several clinical types the most common is leukoplakia. The risk factors include tobacco and excess alcohol use and diets low in antioxidants. Studies concerning the management of risk factors related to oral precancer are meager. OBJECTIVES: We investigated the effectiveness of smoking cessation at a dysplasia clinic among patients followed up for at least for 12 months. METHODS: Data from case notes relating to 180 patients with white and red patches of oral mucosa (excluding other benign disorders confirmed by biopsy findings) attending a dysplasia clinic at a teaching hospital in London and seen by one consultant between 1993 and 2003 were transcribed. Effect of referring to a smoker's clinic to receive specialist help was evaluated against brief advice given at the dysplasia clinic +/- medications. RESULTS: The mean age at the first visit was 48.5 years (+/-12.5), 65% were male, and 88% were white European. One hundred and sixty-two patients (90%) had used tobacco and 83% were current smokers. Of the smokers 95% had smoked over 10 years, the majority smoking over 10 cigarettes per day. Nine were alcohol misusers including two binge drinkers. One hundred and forty-six were diagnosed with oral leukoplakia, 16 with non-homogeneous types (speckled or nodular). Three patients were diagnosed with an erythroplakia. Nineteen per cent exhibited the presence of dysplasia and one subject had in situ carcinoma. Five patients in the sample quit smoking prior to arrival in the dysplasia clinic. Twenty-seven cases (20%) with oral leukoplakia quit smoking while registered as a patient at the dysplasia clinic: 17 of 100 subjects quit with brief advice +/- medications and 10 of 30 following referral to the smoker's clinic. The difference between the two groups was significant for point prevalence abstinence at the last visit to the clinic (minimum 12 months follow up). Out of a total of 180 precancer cases managed in the dysplasia clinic (mean follow up 4.2 years) three patients subsequently developed invasive carcinoma during follow up. CONCLUSIONS: Smoking cessation needs to be an integral component of management of cases attending a dysplasia clinic and referring to smoker's clinics could help to improve the effectiveness of managing patients with oral precancer to quit smoking.