口腔粘膜癌变过程中细胞角蛋白CK10和CK13的变化

目的：探讨细胞角蛋白ＣＫ１０和ＣＫ１３在口腔粘膜癌变过程的各阶段组织中的分布和表达强度。方法：用ＬＳＡＢ免疫组化染色方法对口腔正常粘膜、上皮单纯增生、上皮异常增生和口腔磷癌切片进行染色,光镜观察。结果：正常颊粘膜和口底舌腹粘膜基底上层ＣＫ１０表达阴性,ＣＫ１３表达强阳性;上皮过度不全角化时,ＣＫ１０表达可为阳性,ＣＫ１３表达减少;上皮过度正角化时,ＣＫ１０在基底上层呈强阳性表达,ＣＫ１３表达进一步减少甚至缺失。随上皮异常增生程度加重,基底上层细胞ＣＫ１０和ＣＫ１３表达减少甚至缺失。在口腔浸润癌中,不管分化程度如何,ＣＫ１３均表达阴性,而ＣＫ１０在分化较好的癌细胞及癌巢中呈阳性表达。结论：ＣＫ１３表达减少或缺失可作为口腔癌前病变诊断的辅助指标,ＣＫ１０可为口腔癌的分化程度及其预后判定提供帮助。     

人口腔上皮鳞状细胞癌发生发展过程中Bcl-2蛋白表达的研究

目的：研究Ｂｃ１－２蛋白表达在口腔鳞状细胞癌发生发展过程中的作用及可能的临床意义。方法：对８５例病变标本采用鼠抗人Ｂｃ１－２蛋白单克隆抗体进行免疫组织化学染色。结果：正常口腔粘膜Ｂｃ１－２免疫组化染色均为阴性,口腔上皮单纯增生、异常增生、鳞癌Ⅰ、Ⅱ、Ⅲ级Ｂｃ１－２蛋白阳性表达率分别为１８．７５％、５２．１７％、１８．１８％、２２．２２％和５３．３３％。口腔粘膜异常增生Ｂｃ１－２蛋白阳性表达率显著高     

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。     

抗氧化蛋白Prx1在口腔黏膜白斑中的表达

目的检测抗氧化蛋白Prx1和DNA氧化损伤标记物8-OHdG在口腔黏膜白斑中的表达,探讨Prx1在口腔黏膜白斑中的作用。方法选择40例口腔黏膜白斑,包括单纯增生10例,白斑伴上皮轻度异常增生15例,白斑伴上皮中度异常增生15例,正常口腔黏膜10例。采用免疫组织化学染色方法,分别检测Prx1、8-OHdG在黏膜中的表达。结果口腔黏膜白斑伴上皮中度异常增生组Prx1和8-OHdG染色的MOD值均高于正常组、白斑单纯增生组、白斑伴上皮轻度异常增生组,且差异有统计学意义(P0.01)。结论 Prx1与口腔黏膜白斑的发病有关,口腔黏膜白斑的发生可能与氧化损伤有关。     

Prx1 overexpression in human oral leukoplakia

目的 检测抗氧化蛋白Prx1和DNA氧化损伤标记物8-OHdG在口腔黏膜白斑中的表达,探讨Prx1在口腔黏膜白斑中的作用.方法 选择40例口腔黏膜白斑,包括单纯增生10例,白斑伴上皮轻度异常增生15例,白斑伴上皮中度异常增生15例,正常口腔黏膜10例.采用免疫组织化学染色方法,分别检测Prx1、8-OHdG在黏膜中的表达.结果 口腔黏膜白斑伴上皮中度异常增生组Prx1和8-OHdG染色的MOD值均高于正常组、白斑单纯增生组、白斑伴上皮轻度异常增生组,且差异有统计学意义(P<0.01).结论 Prx1与口腔黏膜白斑的发病有关,口腔黏膜白斑的发生可能与氧化损伤有关.     

口腔粘膜鳞癌发生过程中Bax蛋白的表达

目的：初步探讨Ｂａｘ基因蛋白产物Ｂａｘ蛋白在口腔粘膜癌前损害发生发展过程中的作用及变化的规律。方法：分别选出正常口腔占膜、上皮单纯增生、上皮轻度异常增生、上皮中度异常增生、上皮重度异常增生、鳞状细胞癌标本共３８例,采用免疫组织化学染色技术－－酶标链亲和素生物素法（ＬＳＡＢ）染色并进行光镜下观察。结果：光镜下可见,各阶段均有Ｂａｘ蛋白表达,为细胞浆阳性,从正常口腔粘膜组织、上皮单纯增生到中度上皮异常     

口腔扁平苔藓上皮异常增生的初步研究

对６９５例口腔扁平苔藓进行了统计分析，其中１８例（２．５８％）伴有上皮异常增生。轻度上皮异常增生８例，中度上皮异常增生７例，重度上皮异常增生３例。抗细胞核增殖抗原单克隆抗体免疫组织化学染色，可以清楚地反映不同程度的上皮异常增生情况，本研究支持口腔扁平苔藓可以癌变的观点。     

口腔粘膜上皮异常增生和鳞癌组织中凋亡蛋白Bax的表达研究

目的 研究凋亡相关蛋白Ｂａｘ在口腔正常粘膜、上皮异常增生和鳞癌组织中表达及意义。方法 采用免疫组化方法检测１０例正常粘膜、１０例单纯性增生上皮、３２例异常增生上皮１９例高分化鳞癌、９例低分化鳞癌石蜡包理样本中Ｂａｘ的表达。结果 正常粘膜中见Ｂａｘ弱表达局限于角化层。上皮单纯增生时Ｂａｘ表达较正常组增强,轻度异常增生时反面较单纯增生下降,随异常增生程度加重,Ｂａｘ明显增加。癌变时Ｂａｘ表达较正常组增     

癌前病变口腔上皮中细胞粘附分子CD44v3和CD44v6表？…

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ＣＤ４４３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。随上皮守生程度加重，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     

口腔鳞癌及癌前病变中TGFβ的表达

目的：研究转化生长因子β（TGFβ）在口腔鳞癌及新癌病变中的表达特点。方法：免疫组织化学染色。结果：TGFβ的阳性表达见于癌前上皮分化良好的区域，而上皮的增殖区则为阴性表达。随着上皮由单纯性增生－轻度异常增生－中度异常增生－重度异常增生－磷癌的转变，TGFβ1的表达逐渐减少以及消失。结论TGFβ与口腔鳞癌的发生有着密切的关系。TGFβ1自分泌的减少有利于癌前、上皮的癌变及鳞癌的形成。     

细胞角蛋白CK19在口腔粘膜癌变过程中的变化

目的：探讨口腔粘膜癌变过程中CK19的变化。方法：收集正常口腔粘膜、上皮单纯增生、上皮异常增生和口腔鳞癌活检标本共53例，用免疫组化、电泳和Western杂交方法研究上皮中CK19的表达。结果：CK19表达于有上皮异常增生的复层鳞状上层和口腔鳞癌尤其是低分化鳞癌的癌细胞中。随病变程度加重，CK19表达的阳性率，表达强度和占细胞角蛋白构成比显著增加。结论：CK19表达于粘膜上皮的基底上层可作为口腔癌前病变的辅助标志，CK19表达增加是 口腔粘膜病变过程中的早期事件。     

Immunohistochemical evaluation of expression of cytokeratin 19 in different histological grades of leukoplakia and oral squamous cell carcinoma.

Recent progress in understanding the biology of keratins together with the development of monoclonal antibodies to individual keratin proteins provide the foundation for studying the keratin expression in normal and pathological oral epithelia. Cytokeratin (CK) alterations have been reported in carcinomas and these have been associated with specific aspects of tumour behaviour. Immunohisto-chemistry with monospecific CK19 antibody was used to study the expression pattern in normal mucosa, dysplasias, and oral squamous cell carcinomas (OSCC). In non-keratinzed normal mucosa, CK19 was detected in the basal cell layer, while in dysplasias (diagnosed in H and E stained sections, mild-severe) stained strongly for CK 19 in the basal and supra basal cell layers indicating layer specificity for CK 19 expression. In OSCC, in the number of CK19 labelled cells increased from well to poorly differentiated tumour. Thus the results of the present study indicate an alteration in synthesis of keratin proteins when exposed to carcinogens.     

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。     

CD147和Ki-67在口腔黏膜白斑和鳞癌组织中的表达及意义

目的：观察CD147和ki-67在口腔正常黏膜、白斑和鳞癌组织中表达的变化,阐明CD147在口腔癌发病机制中的作用。方法：采用免疫组织化学法检测10例正常口腔黏膜、20例白斑伴上皮异常增生上皮和40例鳞癌组织中CD147及Ki-67的表达变化。结果：CD147在正常黏膜阴性表达,白斑和鳞癌组上皮均显著表达CD147;正常组Ki-67表达主要位于上皮棘层,鳞癌组织中Ki-67阳性细胞分布广泛,有大部分侵入固有层中。结论：口腔黏膜发生癌前病变时,即出现CD147表达阳性,随着Ki-67阳性细胞数的增多,癌变细胞增殖不断加强,两者共同作用促进鳞癌的发展。     

Assessment of p63 expression in oral squamous cell carcinomas and dysplasias

OBJECTIVES: p63, a p53 homologue, may be associated with tumorigenesis in epithelial tissues through its inhibition of p53 transactivation functions. We sought to determine the pattern and levels of p63 expression in oral dysplasias and carcinomas using standard immunohistochemical staining. We also assessed and compared expression of p53 and a cell proliferation marker in these lesions. STUDY DESIGN: This retrospective cross-sectional survey (n=67) included hyperkeratosis (10), mild dysplasia (9), moderate dysplasia (11), severe dysplasia/in situ carcinoma (10), squamous cell carcinoma (SCC) (22 [9 well differentiated, 7 moderately differentiated, 6 poor differentiated]), and normal mucosa (5). Serial sections were stained immunohistochemically with antibodies to p63 (4A4 recognizing all p63 isotypes), p53 (DO-7), and Ki-67 (MIB-1) proteins. In preinvasive lesions, both the percentage of positive cells and staining patterns (negative, basal, suprabasal) were assessed. In oral SCCs, the percentage of positive cells was assessed. Statistical analysis was done using the Tukey-Kramer multiple comparisons test. RESULTS: A suprabasal p63 staining pattern was evident in keratinocyte nuclei in the entire range of noninvasive lesions studied, including normal mucosa. Most nuclei in invasive SCCs stained positive. When all grades of dysplasia were combined, the percent of p63 positive cells was significantly greater than hyperkeratosis (P < .01), and well-differentiated SCC (P < .001). Moderately differentiated SCC had statistically significant more positive cells than well-differentiated SSC (P < .01). Comparison of serial sections showed different p63 staining patterns compared to p53 or Ki-67 staining patterns. CONCLUSIONS: We conclude that p63 is expressed in oral carcinomas and dysplasias, as determined by immunohistochemical staining with a primary antibody to all isotypes. Neither staining pattern nor percentage of stained cells could be used to differentiate the lesions studied. The statistically significant differences found between some groups are not likely to be of diagnostic value. p63 is not coexpressed with p53 expression or Ki-67 suggesting functional independence. When antibodies to the p63 isotypes become available, oral dysplasias and carcinomas should be reassessed.     

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.     

端粒酶蛋白催化亚基(hTRT)mRNA在口腔鳞癌形成过程中的表达

目的:观察端粒酶催化蛋白基因hTRT在口腔粘膜恶性转化不同阶段中的表达,探讨其与口腔粘膜细胞恶性程度的关系。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8例、口腔粘膜鳞癌30例。结果:正常口腔粘膜、上皮单纯性增生组织中hTRT的mRNA表达较弱,阳性信号仅局限于上皮基底层及副基底层间,阳性率21.4%(3/14);上皮异常增生中hTRTmRNA阳性表达见于多层上皮细胞,并随细胞异形性增高而表达增强,阳性率46.7%(14/30);口腔粘膜鳞癌组织中hTRT的mRNA有较强阳性表达,阳性率81.6%(31/38)。结论:端粒酶hTRT基因的表达与口腔粘膜细胞的恶性程度密切相关,端粒酶的重新激活在口腔鳞癌的形成过程中起了关键性作用     

细胞角蛋白19和间隙连接蛋白43在4-亚基硝氧喹啉诱发大鼠舌黏膜癌变过程中表达的研究

目的 研究4-亚基硝氧喹啉（4NQO）诱发大鼠口腔黏膜癌变过程中细胞角蛋白19（CK19）和间隙连接蛋白43（Cx43）的表达,探讨口腔黏膜癌变过程中CK19与Cx43的相关性。方法 利用4NQO诱导SD大鼠的口腔黏膜癌变,运用免疫组织化学的方法检测CK19、Cx43在口腔黏膜癌变过程中各阶段的动态变化。结果 在大鼠正常舌黏膜组织中,CK19阳性染色的细胞散在分布于黏膜基底层;随着大鼠舌黏膜上皮异常增生程度的增加,CK19表达于黏膜基底上层;在口腔鳞状细胞癌（OSCC）组织中,CK19阳性染色细胞分布在黏膜各层。CK19在正常舌黏膜、轻度上皮异常增生、中度上皮异常增生、重度上皮异常增生、OSCC组织中阳性表达率分别为30.00%、50.00%、58.33%、80.00%、91.67%,差异有统计学意义（P<0.05）。在正常舌黏膜中Cx43蛋白主要表达于大鼠舌黏膜上皮细胞的细胞膜上,上皮的基底层、棘层和颗粒层呈阳性染色。随着大鼠舌黏膜上皮异常增生程度的增加,Cx43的表达明显下降。Cx43在正常舌黏膜、轻度上皮异常增生、中度上皮异常增生、重度上皮异常增生、OSCC组织中阳性表达率分别为100.00%、85.71%、66.67%、40.00%、33.33%,差异有统计学意义（P<0.05）。结论 在大鼠舌黏膜癌变过程中,CK19蛋白表达水平随病变程度加重显著升高,提示CK19与口腔上皮细胞的癌变有关;Cx43蛋白表达水平随病变程度加重显著下降,Cx43表达下降是口腔黏膜癌变的早期事件。CK19与Cx43蛋白表达呈负相关,CK19和Cx43的联合检测对OSCC的早期诊断有重要的作用,有利于提高OSCC早期诊断的灵敏度和特异性。     

人牙龈结合上皮、口腔龈上皮及沟内上皮中细胞角蛋白的表达

目的 检测人牙龈上皮的细胞角蛋白(CK)谱，探讨结合上皮(JE)与口腔龈上皮(OE)、沟内上皮(SE)的不同。方法 5例人磨牙及前磨牙牙龈颊舌向石蜡切片，采用免疫组化SP法行CK5／6、7、8／18、10／13、16、17、19、20染色。结果 CK7、17在3种上皮中均无表达；CK5／6、20在3种上皮的基底上层(尤其是近表层)为弱阳性及阳性表达，基底层无表达；CK10／13、16在JE全层均有表达，在OE和SE仅限于基底上层，其中CK10／13为强阳性，CKl6为弱阳性及阳性；CK19在JE全层强阳性，在OE和SE仅限于基底层，JE和SE分界明显；CK8／18与CK19相似，只是表达较弱，近基底层的基底上层也有少量表达。结论JE是一种不同于OE和SE的特殊低分化上皮，CK19可作为JE的特征性标记物区别于OE和SE，CK10／13、16可用于体外培养的上述3种细胞的鉴别。