【作者】 韩玉玲；

【导师】 高义军；

【作者基本信息】 中南大学 ， 口腔临床医学， 2008， 硕士

【摘要】 目的:研究口腔粘膜下纤维性变（oral submucous fibrosis,OSF）及其伴发口腔癌组织中MDM2、p21^WAF/CIP1蛋白的表达情况,探讨MDM2、p21^WAF/CIP1在OSF癌变机制中的作用。方法:选取经临床及病理确诊OSF患者44例,其中早期14例,中期15例,晚期15例,15例OSF伴发口腔癌组织,同时设置8例无口腔粘膜疾患、无烟、酒、槟榔等不良嗜好的健康志愿者的口腔粘膜相应组织为正常对照。免疫组化SP法检测上述各组MDM2、p21^WAF/CIP1蛋白的表达,并分析它们之间的相关性。结果:1.MDM2蛋白在正常口腔粘膜中阴性表达,在OSF及OSF伴发口腔癌组织中阳性表达。OSF中期、晚期组及OSF伴发口腔癌组显著高于正常对照组（P＜0.01）;OSF伴发口腔癌组显著高于OSF各组（P＜0.01）;OSF中期、晚期组显著高于OSF早期组（P＜0.01）。2.p21^WAF/CIP1蛋白在正常口腔粘膜呈阳性表达,OSF组织及OSF伴发口腔癌组织中阳性表达逐渐减少。OSF组及OSF伴发口腔癌组中p21^WAF/CIP1阳性表达显著低于正常对照组（P＜0.01）;OSF伴发口腔癌组与OSF早、中期组比较,阳性表达减少,差异有显著性（P＜0.01）,与OSF晚期组比较,差异显著（P＜0.05）。3.MDM2和p21^WAF/CIP1蛋白在OSF及OSF伴发口腔癌组织中的表达呈显著负相关,Pearson相关系数r=-0.763,P＜0.01。结论:1.OSF伴发口腔癌组织中MDM2蛋白阳性表达率明显高于OSF组织,推测过表达的MDM2蛋白可能通过促进p53蛋白经泛酸途径降解,野生型p53的抑癌活性丧失,导致肿瘤发生。2.OSF伴发口腔癌组织中p21^WAF/CIP1蛋白阳性表达率明显低于OSF组织,推测p21^WAF/CIP1蛋白的减少失去对细胞增殖的抑制作用,导致肿瘤的发生。3.MDM2、p21^WAF/CIP1蛋白在OSF及伴发口腔癌组织中的表达呈显著负相关,表明p21^WAF/CIP1可能受MDM2抑制作用,共同参与OSF的痛变。更多还原

【Abstract】 Objective:To investigate the expression of MDM2 and p21^WAF/CIP1protein in oral submucous fibrosis（OSF）and oral submucous fibrosis concomitant with oral squamous cell carcinoma（OSCC）,and to evaluate their possible roles in carcinogenesis of OSF.Method:MDM2 and p21^WAF/CIP1protein expressions were assessed in 44 cases of OSF,15 cases of OSF concomitant with OSCC and 8 cases of normal control tissues via SP immunohistochemistry with the MDM2 and p21^WAF/CIP1rat anti-human monoclonal antibody.Statistic analysis was performed to figure out their expressions or correlation among their expressions and clinicopathological parameters of the patients with OSF concomitant with OSCC.Results:Positive MDM2-immunoreactivities were seen in early,middle,late stage OSF and OSF concomitant with OSCC,but negative in normal contol group.Positive p21^WAF/CIP1-immunoreactivities were seen in normal contol tissues and OSF,however.The expression of MDM2 increased（P＜0.01）,while the expression of p21^WAF/CIP1decreased（P＜0.01）in OSF concomitant with OSCC compared with those in normal control tissues.The expression of MDM2 in OSF concomitant with OSCC tissues was significantly higher than that in OSF and normal oral tissues（P＜0.01）.The expression of MDM2 at middle and late stages increased when compared with early stage（P＜0.01）. There was no significantly difference between middle and late stage of OSF.The expression of p21^WAF/CIP1in OSF concomitant with OSCC tissues was significantly lower than that in the early and middle stages of OSF tissues（P＜0.01）.The expression of p21^WAF/CIP1in OSF concomitant with OSCC tissues was significantly lower than that in the late stage of OSF tissues（P＜0.05）.There was a statistic inverse correlation between MDM2 and p21^WAF/CIP1expressions in OSF and OSF concomitant with OSCC tissues（r=-0.763,P＜0.01）.Conclusion:The frequency of MDM2 protein positive expression in OSF concomitant with OSCC was obviously higher than thant in OSF tissues. It may act as an important role in carcinogenesis of OSF.The cyclin-dependent kinase inhibitor p21^WAF/CIP1protein positive expression was obviously lower in OSF concomitant with OSCC than in OSF.There was a statistic inverse correlation between MDM2 and p21^WAF/CIP1 expressions in OSF and OSF concomitant with OSCC tissues.MDM2 could decrease the expression of p21^WAF/CIP1protein in OSF concomitant with OSCC.This study supports the hypothesis that they may contribute to the carcinogenesis of OSF.更多还原