Epstein-Barr virus in oral proliferative verrucous leukoplakia and squamous cell carcinoma: A preliminary study

The aim of this study was to analyze proliferative verrucous leukoplakia (PVL) and oral squamous cell carcinoma (OSCC) for the possible presence of Epstein-Barr virus (EBV). We studied three groups: Sub-Group 1 was composed of 10 patients with PVL, (6 of whom had developed OSCC); Sub-Group 2 comprised 5 patients with OSCC but no preceding PVL; and Sub-Group 3 were 5 controls with clinically normal oral mucosa. Oral biopsies from all cases were examined for Epstein-Barr virus (EBV) by nested PCR. EBV was detected in 60% of Sub-Group 1 patients (PVL ) and in 40% of Sub-Group 2 (OSCC), but in 0% of Sub-Group 3 (controls).     

口腔白斑及鳞癌中Rb、P53蛋白的表达

目的 :探讨抑癌基因p5 3 、Rb蛋白产物在口腔白斑及鳞癌中的表达。方法 :用免疫组化法检测 2 0例口腔白斑 (OLK)、3 3例鳞癌 (OSCC)组织中P5 3 及Rb蛋白的表达。结果 :Rb蛋白在OLK、OSCC中的表达较正常口腔黏膜组增强 ,但无显著性差异 ;突变型P5 3 蛋白的表达在OLK即已出现 ,且随着细胞异常增生程度的增高而增强 ,在OSCC中其阳性表达率高达 80 %。结论 :p5 3 基因突变、P5 3 蛋白过度表达与OSCC的发生发展密切相关 ;OSCC的发生可能涉及Rb、p5 3 细胞周期生长抑制反馈调节通路的异常     

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。     

Rapid progression of an idiopathic leukoplakia to a proliferative verrucous leukoplakia lesion and then squamous cell carcinoma

The article reports a case of oral proliferative verrucous leukoplakia (OPVL) in a 76-year-old woman, underscoring how an otherwise inconspicuous white plaque lesion can rapidly turn into a phase of verrucous carcinoma and subsequently squamous cell carcinoma.     

Midkine expression in oral squamous cell carcinoma and leukoplakia

J Oral Pathol Med (2012) 41 : 21–26 Background: Midkine (MK), a 13‐kDa heparin‐binding growth factor, is overexpressed in various human cancers. However, its role in the development and progression of oral cavity squamous cell carcinoma (OCSCC) is still unclear. Thus, the aim of this study was to evaluate the expression of MK in samples of OCSCC, leukoplakia, and healthy oral mucosa (control). Methods: Surgically excised specimens from patients with primary OCSCC (n = 28) were immunostained for MK, Ki‐67, PCNA, p53, bcl‐2, Bax, and CD31. Besides this, MK expression was also investigated in leukoplakia and normal oral mucosa. The relationship of MK⁺ cells with clinical parameters (tumor location, tumor size, lymph node metastasis, and survival) and microscopic parameters (WHO histological grading, intensity of inflammation, proliferation index, apoptosis, and angiogenesis) was also evaluated. Results: The results showed that MK expression was increased in OCSCC in relation to leukoplakia and normal mucosa. Furthermore, MK expression was increased in late‐stage tumors (T3/T4) compared with early‐stage lesions (T1/T2). MK‐positive lesions also showed increased expression of the anti‐apoptotic protein bcl‐2. Conclusion: OCSCC, particularly late‐stage tumors, exhibits increased MK expression, which may be involved in tumor progression via upregulation of anti‐apoptotic genes, as shown by the augmented bcl‐2 positivity in MK‐positive tumors.     

口腔白斑和鳞癌中p16基因甲基化的研究

目的　探讨p16基因甲基化在口腔黏膜白斑癌变中的作用。方法　采用甲基特异性PCR技术检测了 10例正常口腔黏膜、20例白斑上皮单纯增生、11例白斑上皮轻度异常增生、10例白斑上皮中度异常增生、9例白斑上皮重度异常增生、10例鳞癌Ⅰ级、12例鳞癌Ⅱ级、8例鳞癌Ⅲ级标本的p16基因甲基化情况。结果　上述各组的p16基因甲基化率分别为 0、5%、18%、10%、22%、50%、42%和 63%。p16基因甲基化率与口腔黏膜组织恶性度显著正相关,并与p16蛋白缺失表达率呈显著正相关关系(rp=0 777 , rs=0 960, P<0 001)。结论　p16基因甲基化状态可作为白斑癌变和口腔鳞癌诊断的分子生物学重要标志之一。     

口腔疣状癌与口腔鳞状细胞癌差异基因表达的对比分析

目的研究口腔疣状癌与口腔鳞癌组织基因的差异表达，探讨口腔疣状癌（oral Verrucous carcinoma，OVC）与口腔鳞癌（oral squamous cell carcinoma，OSCC）的基因学基础。方法应用cDNA芯片技术对4例OVC和4例OSCC组织mRNA检测，通过芯片杂交、生物信息学处理，找出两者间差异表达基因。结果BioStarH-40芯片发现差异表达基因593条，差异表达基因占15．2％，其中表达增强283条（显著增强59条），表达降低310条（显著降低98条）。结论OVC与OSCC基因表达比较，差异有统计学意义，这些差异可能在各自不同的生物学行为中起重要作用。     

Aggressive,multifocal oral verrucous leukoplakia: proliferative verrucous leukoplakia or not?

BACKGROUND: Some oral verrucal lesions may constitute parts of the clinicopathological spectrum of proliferative verrucous leukoplakia (PVL). Because of its idiopathic yet sinister nature, it is possible that PVL may exist in other populations. The aim of this study was to review the clinicopathological features of persistent, multifocal, oral verrucal lesions in Malaysian population. METHODS: Patients with multifocal oral verrucal lesions were selected from surgical and histopathological records. RESULTS: Nine patients of diverse ethnicity with 43 biopsies were reviewed. The mean age at the presentation was 62 years. The most frequent sites affected were gum, sulci, cheek and tongue. Indulgence in risk habits was reported in about 70% of patients. Four cases developed multifocal carcinoma from multifocal leukoplakia. CONCLUSIONS: In retrospect, none of the cases fulfilled the original PVL criteria, although three cases were suggestive of PVL. Nevertheless, these findings do not necessarily preclude the existence of PVL as a clinicopathological entity in Malaysian population.     

p53和增殖细胞核抗原在口腔白斑和口腔鳞状细胞癌中的表达及意义

目的 检测正常口腔黏膜、口腔黏膜白斑和口腔鳞状细胞癌(OSCC)中p53和增殖细胞核抗原(PCNA)表达,探讨p53和PCNA在OSCC癌变过程中的规律及相关性.方法 口腔黏膜白斑标本20例、OSCC标本31例及正常口腔黏膜10例,采用免疫组化SP法检测其p53和PCNA的表达,应用SPSS 11.0软件包对结果进行χ2检验、单因素方差分析和线性回归分析.结果 p53在正常黏膜组、白斑组与鳞状细胞癌组的表达率分别为0%、35%和77.4%,PCNA在上述三组中表达率分别为30%、70%和96.8%,两种表达的组间比较差异有统计学意义(P<0.05);p53蛋白与PCNA表达呈正相关(P<0.01).结论 p53基因和PCNA表达水平均与OSCC发展进程密切相关.     

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。     

TFAR19在口腔白斑和口腔鳞癌中表达的研究

目的研究凋亡相关基因tfar19在口腔正常黏膜、口腔白斑和口腔鳞癌组织中的表达及意义。方法采用免疫组织化学方法检测17例正常口腔黏膜、60例口腔白斑,30例口腔鳞癌组织标本中TFAR19蛋白的表达。结果①口腔正常黏膜组TFAR19染色阳性率为88.2%,白斑组TFAR19染色阳性率为63.3%,口腔鳞癌组TFAR19染色阳性率为30%,3组间染色阳性率分别有统计学差异(分别为P≤0.05)。应用Crosstabs相关性统计分析,TFAR19染色阳性率与组织病变恶性度显负相关(r=-0.997,P<0.05)。②口腔正常黏膜、口腔白斑和口腔鳞癌组织的TFAR19细胞染色强度指数分别为199.34±25.33、130.23±19.21,和59.44±13.83,各组间分别有显著性差异。结论tfar19基因在口腔黏膜上皮成癌过程中的确发挥着重要的作用,并且可以推测tfar19基因的表达缺失发生在肿瘤形成的早期。     

Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma

Objectives: Oral leukoplakia (OL) is the main potentially malignant disorder and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. This study aimed to evaluate the presence of stromal myofibroblasts in OL and OSCC. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between histologically high- and low-invasive OSCC were also assessed. Study Design: A total of 30 OL and 41 OSCC from archival formalin-fixed, paraffin-embedded specimens were evaluated. 10 samples of normal oral mucosa were used as a control. Myofibroblasts were identified by immunohistochemical detection of alpha smooth muscle actin and its presence was classified as negative, scanty or abundant. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between high- and low-invasive OSCC were analyzed using the Mann-Whitney test. Results: Myofibroblasts were not detected in normal oral mucosa and OL, whatever its histological grade. In OSCC, the presence of stromal myofibroblasts was classified as negative in 11 (26.8%), scanty in 15 (36.6%), and abundant in 15 samples (36.6%). The presence of stromal myofibroblasts was statistically higher in high-invasive OSCC than in low-invasive OSCC (p<0.05). Conclusions: Stromal myofibroblasts were not detected in OL, indicating that these cells are not important during oral carcinogenesis. Nevertheless, stromal myofibroblasts were heterogeneously detected in OSCC and its presence was higher in tumors with a more diffuse histological pattern of invasion. These findings suggest that myofibroblasts are associated with the creation of a permissive environment for tumor invasion in OSCC.     

Proliferative verrucous leukoplakia: high incidence of gingival squamous cell carcinoma

BACKGROUND: Proliferative verrucous leukoplakia (PVL) is a multifocal and progressive lesion of the oral mucosa, often associated with papillomavirus, seen mainly in older females, and characterized by a high recurrence rate and high rate of transformation into verrucous or oral squamous cell carcinoma (OSCC). The aim of this study was to analyse the clinical characteristics of a substantial group of patients with PVL, evaluating the characteristics of those who developed cancer, and comparing them with a group of patients with OSCC but no preceding PVL. METHODS: A group of 30 patients with PVL was studied for the clinical aspects and characteristics, age, sex, location, recurrence, the appearance of new lesions, and the frequency of development of oral cancer. A disease control group was formed with 110 patients with OSCC chosen randomly from among those treated in the same Service in this period of time. The patients were grouped as PVL and no cancer (Group 1); PVL developing cancer (Group 2) and patients with OSCC without clinical lesions associated with PVL (Group 3). RESULTS: The average age of the PVL patients (Groups 1 and 2 combined) was 70.97 +/- 12.73 years, of which 80% were women. Only 23.3% were cigarette smokers. The area most frequently affected with PVL was the lower gingiva. Recurrence after treatment was seen in 86.7%, and new lesions appeared in 83.3%. Many (63.3%) developed cancer (Group 2). Comparison of Groups 2 and 3 patients showed that those with PVL developing cancer were more likely to develop gingival carcinoma and also to be older, more often females, and less likely to smoke tobacco. CONCLUSION: Cancer developing in patients with PVL manifested particularly on the gingiva.     

PTEN、p27在口腔粘膜白斑和口腔癌组织中的表达及意义

目的　探讨抑癌基因PTEN、p2 7在口腔粘膜白斑 (oralleukoplakia ,OLK)和口腔癌 (oralsquamouscellcancer,OSCC)组织中的蛋白表达及意义。方法　应用免疫组化S -P法检测 10例正常口腔粘膜、2 5例口腔粘膜白斑 (其中白斑伴上皮异常增生 15例 ,白斑不伴上皮异常增生 10例 )及 32例口腔癌组织中抑癌基因PTEN和p2 7的蛋白表达情况。结果　正常口腔粘膜和白斑不伴上皮异常增生组织中PTEN和 p2 7蛋白全部阳性表达 ;白斑伴上皮异常增生组织中PTEN和 p2 7蛋白阳性表达率分别为93.3%、73.3%。OSCC组织中PTEN蛋白阳性表达率为71.9% ,其中高、中、低分化OSCC组织中PTEN蛋白阳性表达率分别为 85 .7%、75 %和 33.3% ,统计学分析表明PTEN在OSCC组织中的蛋白表达与组织分化程度明显相关 (P <0 .0 5 )。OSCC组织中 p2 7蛋白的阳性表达率为4 0 .6 % ,其中高、中、低分化OSCC组织中p2 7蛋白的阳性表达率分别为 4 2 .9%、4 1.7%和 33.3% ,统计学分析表明p2 7在OSCC组织中的蛋白表达与组织分化程度无明显相关 (P >0 .0 5 )。结论　OSCC组织中PTEN和 p2 7蛋白的阴性表达率较高 ,说明PTEN和 p2 7基因突变或缺失在OSCC的发生发展过程中起重要作用。     

Bcl-2、MDM2和p21在口腔白斑和口腔鳞状细胞癌中的表达水平研究

目的：了解Bcl-2、MDM2、p21在人口腔正常黏膜、白斑、鳞状癌细胞中的表达情况.方法：采用免疫组化二步法检测15例人正常口腔黏膜、15例单纯增生性白斑、10例异常增生性白斑,25例口腔鳞癌中Bcl-2、MDM2和p21蛋白的表达情况.结果：Bcl-2、MDM2蛋白在异常增生性白斑和口腔鳞癌中的表达明显高于正常口腔黏膜上皮细胞;p21蛋白在异常增生性白斑和口腔鳞癌中的表达明显低于正常口腔黏膜上皮细胞.结论：Bcl-2、MDM2和p21三者与口腔黏膜癌变具有相关性.     

口腔白斑和鳞癌中P_(53)基因突变的PCR─SSCP分析

本实验应用聚合酶链反应－单链构象多态性（PCR—SSCP）分析技术对5例正常口腔粘膜、22例白斑和30例鳞癌中P53基因突变情况进行检测。结果表明，轻、中、重度异常增生白斑，无和有淋巴结转移鳞癌P53突变率为12．5％，37．5％，50．0％，64．3％和75．0％，正常粘膜无一例阳性，白斑和鳞癌间P53变化有显著性差异（P＜0．05）。P53突变与鳞癌有否淋巴结转移无关。