端粒酶hTR基因在口腔癌前病变及鳞癌中的表达

目的探讨端粒酶ｈＴＲ基因在口腔癌前病变及鳞癌中的表达。方法用原位杂交技术检测８２例标本,其中正常口腔粘膜７例,上皮单纯性增生７例,上皮异常增生３０例,原位癌、鳞癌３８例。结果正常口腔粘膜及上皮单纯性增生组织中ｈＴＲ表达较弱,阳性细胞主要位于基底层,检出率２８．５６％（４／１４）。癌前病变中随着异常增生程度的增加,ｈＴＲ表达逐渐增强,阳性细胞逐步由基底层向棘层波及,检出率６０％（１８／３０）。原位癌及鳞癌均有较强的ｈＴＲ表达,检出率为８１．５８％（３１／３８）。结论端粒酶的激活可能出现在口腔癌前病变的晚期阶段,在口腔鳞癌的形成过程中起了关键性作用。     

口腔鳞癌中hTRT mRNA的表达及其与PCNA关系的探讨

目的：探讨端粒酶逆转录酶（hTRT)在口腔鳞癌、癌旁组织的表达及其与增殖细胞核抗原（PCNA）之间的关系。方法：用原位杂交技术及免疫组化方法检测52例口腔鳞癌标本。结果：正常癌旁上皮、上皮异常增生组织及鳞癌hTRT mRNA阳性率分别为20％、41．7％、82．7％。PCNA阳性组与阴性组间hTRT表达水平有显著差异（P＜0．05）。结论：hTRT在口腔鳞癌发生、发展中起重要作用，hTRT与PCNA阳性表达呈正相关，表明hTRT激活细胞多处于高增殖状态。     

口腔粘膜白斑和鳞癌组织凋亡相关蛋白Bcl—2和Bax的表达研究

目的：研究凋亡相关蛋白Ｂｃｌ－２,Ｂａｘ在口腔正常粘膜,上皮异常增生和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１０例正常口腔粘膜,１０例单纯性增生上皮,３０例异常增生上皮,３３例鳞癌石蜡包埋样本中Ｂｃｌ－２、Ｂａｘ的表达,结果：Ｂｃｌ－２在正常粘膜,单纯增生和异常增生白斑表达情况基本一致,显弱阳性表达且局限于基底层细胞、鳞癌组织中Ｂｃｌ－２表达明显高于正常组和白斑组（Ｐ〈０．０５）,     

口腔黏膜癌前病变及鳞癌中Fas/FasL的表达研究

目的 :研究凋亡相关基因Fas/FasL在口腔正常粘膜、上皮单纯增生、上皮异常增生和鳞癌中的表达及意义。方法 :采用SABC免疫组织化学方法检测正常口腔粘膜 ( 10例 ) ,上皮单纯增生 ( 8例 ) ,上皮异常增生 ( 2 0例 ) ,鳞癌 ( 32例 )中Fas/FasL的表达。结果 :在正常口腔粘膜中Fas表达于棘层和粒层细胞的胞膜 ;FasL局限于基底层细胞的胞膜和胞浆。上皮异常增生中随异常增生程度的增高 ,Fas表达降低 ;FasL表达增强 ,甚至遍布上皮全层。鳞癌组中Fas表达明显低于正常组 (P <0 .0 5 ) ,且与组织学分级呈正相关 ;FasL表达明显高于正常组 (P <0 .0 5 ) ,且与组织学分级呈负相关。结论 :Fas在调节鳞状上皮细胞自我更新中具有重要作用。Fas表达水平下调 ,FasL上调 ,可能是口腔上皮癌变过程中的一个早期事件。Fas/FasL是肿瘤细胞逃逸肿瘤反应T细胞攻击而获得免疫赦免的重要机制之一。     

口腔粘膜白斑和鳞癌组织凋亡相关蛋白Bcl-2和Bax的表达研究

目的研究凋亡相关蛋白Bcl-2、Bax在口腔正常粘膜,上皮异常增生和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10例正常口腔粘膜,10例单纯性增生上皮,30例异常增生上皮,33例鳞癌石蜡包埋样本中Bcl-2、Bax的表达。结果Bcl-2在正常粘膜、单纯增生和异常增生白斑表达情况基本一致,显弱阳性表达且局限于基底层细胞.鳞癌组织中Bcl-2表达明显高于正常组和白斑组(P＜0.05),且随组织分化程度的降低,Bcl-2的表达逐步加强。Bax在正常粘膜、白斑和鳞癌组中总的阳性率无明显差异,但表达强度不同。正常组Bax弱表达局限于角化层,异常增生白斑组中随异常增生程度的增高,Bax表达加强且遍布上皮全层。鳞癌组织中高分化鳞癌的Bax表达明显高于低分化鳞癌。结论Bax蛋白表达水平代偿性增高是口腔癌前病损发生发展中的早期事件,Bcl-2可能并不参与癌前病变的发生,Bcl-2表达加强和Bax表达下降在促进肿瘤细胞异常增殖的同时,进一步抑制细胞的凋亡导致口腔癌最终的发生和发展。     

端粒酶催化亚基hTRTmRNA在口腔鳞癌中的表达

目的:探讨口腔鳞癌中端粒酶催化亚基hTRTmRNA的表达。方法:应用原位杂交方法,检测hTRTmRNA在65例口腔鳞癌、25例上皮异常增生及20例正常口腔黏膜中的表达。以地高辛标记,常规杂交后处理。阳性对照为口腔鳞癌,阴性对照为不加探针。采用SPSS10.0统计软件进行χ2检验、Kendall相关分析以及成组比较t检验。结果:hTRTmRNA在正常口腔黏膜上皮组织中呈弱表达(4/20、20.0%),在上皮异常增生组织中表达增强(11/25、44.0%),在口腔鳞癌组织中呈强阳性表达(54/65、83.1%)。hTRTmRNA在口腔鳞癌组织与其他各组阳性表达率差异有统计学意义(P<0.01),并呈正相关关系(P<0.01),但正常口腔黏膜与上皮异常增生间差异无统计学意义(P>0.05);各病理类型间,染色强度构成比差异有统计学意义(P<0.01),但正常口腔黏膜与上皮异常增生间差异无统计学意义(P>0.05)。结论:hTRTmRNA的表达与口腔黏膜细胞的恶性转化密切相关,端粒酶基因的重新激活,可能在口腔鳞癌的发生中起着关键作用。     

口腔粘膜癌前病变及鳞癌中RASSF1A基因甲基化与表达的研究

目的 研究RASSF1A基因甲基化状态及其基因表达异常与口腔癌前病变及鳞癌发生发展的关系。方法 采用甲基化特异性PCR（MSPCR）技术检测了10例正常口腔粘膜、8例上皮单纯增生、20例上皮异常增生、32例鳞癌组织中RASSF1A基因甲基化状况；运用逆转录-聚合酶链反应（RT-PCR）研究口腔粘膜癌前病变及鳞癌组织中RASSF1A基因mRNA的表达水平。结果 10例正常口腔粘膜无甲基化。且RASSF1A基因mRNA呈100％表达；8例上皮单纯增生中，有1例甲基化，1例RASSF1A mRNA表达下降；20例上皮异常增生中，有3例甲基化，5例RASSF1A mRNA表达下降；32例鳞癌组织中，有13例甲基化，占40．63％，15例RASSF1A mRNA表达下降或无表达。占46．88％。结论 RASSF1A基因甲基化是口腔癌癌变的早期事件，与口腔鳞癌的发生发展有关。RASSF1A基因甲基化与RASSSF1A基因转录抑制高度相关。     

金黄地鼠颊囊癌变过程中DPC4的表达特征

目的:研究dpc4基因在金黄地鼠颊囊癌变过程中的表达特征,探讨其与口腔鳞癌的发生、发展之间的关系及临床意义。方法:用免疫组化技术检测23例金黄地鼠颊囊正常上皮、21例单纯增生上皮、27例异常增生上皮、25例鳞癌组织中DPC-4的表达。结果:DPC-4在正常黏膜上皮组织的细胞质内呈稳定性、强阳性表达,在细胞质内出现棕褐色颗粒;在单纯增生上皮中表达与正常黏膜组织相似;在上皮异常增生组织表达降低,阳性率为74.1%;在鳞癌中的表达亦明显降低,阳性率为48%,且与正常黏膜、异常增生黏膜相比有显著性差异(P<0.01)。结论:Smad4的缺失促进了口腔黏膜鳞癌发生发展。     

Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders

Oral carcinogenesis is a multi-step process. One possible step is the development of potentially malignant disorders known as leukoplakia and erytroplakia. The objective of this study was to use immunohistochemistry to analyze the patterns of expression of the cell-cycle regulatory proteins p53 and p16(INK4a) in potentially malignant disorders (PMD) of the oral mucosa (with varying degrees of dysplasia) and in oral squamous cell carcinomas (OSCC) to correlate them with the expression of telomerase (hTERT). Fifteen PMD and 30 OSCC tissue samples were analyzed. Additionally, 5 cases of oral epithelial hyperplasia (OEH) were added to analyze clinically altered mucosa presenting as histological hyperplasia without dysplasia. p53 positivity was observed in 93.3% of PMD, in 63.3% of OSCC and in 80% of OEH. Although there was no correlation between p53 expression and the grade of dysplasia, all cases with severe dysplasia presented p53 suprabasal immunoexpression. p16(INK4a) expression was observed in 26.7% of PMD, in 43.3% of OSCC and in 2 cases of OEH. The p16(INK4a) expression in OEH, PMD and OSCC was unable to differentiate non-dysplastic from dysplastic oral epithelium. hTERT positivity was observed in all samples of OEH and PMD and in 90% of OSCC. The high hTERT immunoexpression in all three lesions indicates that telomerase is present in clinically altered oral mucosa but does not differentiate hyperplastic from dysplastic oral epithelium. In PMD of the oral mucosa, the p53 immunoexpression changes according to the degree of dysplasia by mechanisms independent of p16(INK4a) and hTERT.     

口腔黏膜癌前病变癌变过程中端粒酶逆转录酶mRNA和增殖细胞核抗原的表达及其相关性

目的　探讨人端粒酶逆转录酶 (hTERT)mRNA和增殖细胞核抗原 (PCNA)在口腔黏膜癌前病变癌变发生发展中的作用 ,以及hTERTmRNA与PCNA蛋白表达之间的关系及意义。方法　应用原位杂交和免疫组化法对口腔黏膜单纯性增生 (HP)9例 ,轻度异常增生 (LD) 11例 ,中度异常增生 (MD) 10例 ,重度异常增生 (即原位癌 ,CIS) 9例 ,鳞癌 (SCC) 11例 ,进行hTERTmR NA及PCNA蛋白检测 ,结果应用计算机图像分析系统分析。结果　口腔黏膜上皮从HP、LD、MD到CIS、SCC ,hTERT、PCNA蛋白的阳性细胞面积指数及吸光度 (A)值均逐渐上升 ,鳞癌最高。在HP及LD ,hTERT、PCNA阳性细胞主要位于基底层 ,但随着细胞异常增生程度的加重 ,阳性表达细胞从基底层向角化层进展。在高分化鳞癌中 ,主要分布在癌巢周边 ,分化较差的鳞癌则散布于整个肿瘤组织中。PCNA与hTERTmRNA表达呈线性正相关。结论　hTERT与PCNA均参与口腔黏膜癌前病变癌变的发生发展过程 ;PCNA与hTERTmRNA表达的正相关 ,表明hTERT激活细胞多处于高增殖状态。     

Aktuelle Klassifikation der Präkursorläsionen des oralen Plattenepithelkarzinoms

The WHO classification of oral tumours summarizes the precancerous squamous cell lesions under the term epithelial precursor lesions. For the first time three classification schemas that histologically categorize oral epithelial precursor lesions are used analogously. According to the WHO suggestion of 2005 the traditional schema of grading dysplasia as mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in situ continues to be used. In addition the concept of intraepithelial neoplasia is introduced as squamous intraepithelial neoplasia I-III. Squamous intraepithelial neoplasia III (SIN III) combines severe dysplasia and carcinoma in situ. The Ljubljana classification of squamous intraepithelial lesions was originally established to grade laryngeal epithelial precancerous lesions. The clear and succinct nomenclature and the simple clinical utility of the Ljubljana classification have also proven to be useful for oral epithelial precursor lesions: squamous cell (simple) hyperplasia; basal/parabasal cell hyperplasia (analogous to mild dysplasia and to SIN I); atypical hyperplasia (analogous to moderate-severe dysplasia and to SIN I-III and is also called risky epithelium); carcinoma in situ (analogous to WHO carcinoma in situ and to SIN III). Atypical hyperplasia (risky epithelium) and carcinoma in situ are defined as lesions requiring either total excision or close clinical monitoring.     

单层上皮细胞角蛋白在口腔粘膜癌变过程中的表达

目的：探讨单层上皮细胞角蛋白ＣＫ１８和ＣＫ１９作为口腔癌前病变标志的可能性。方法：用ＬＳＡＢ免疫组化染色方法检测ＣＫ１８和ＣＫ１９在福尔马林固定,石蜡包埋的口腔正常粘膜,上皮单纯增生,轻度上皮导演增生,中度上皮异常增生,重度上皮异常增生和口腔鳞癌组织中的分布和表达强度,光镜观察染色切片,结果用秩和检验分析。     

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.