食管癌变过程中p16和FHIT甲基化与蛋白失表达关系的研究

STUDY ON THE RELATIONSHIP OF P16、FHIT METHYLATION AND LOSS OF PROTEIN EXPRESSION IN THE ESOPHAGEAL CARCINOGENESIS

[目的]研究食管癌变过程中p16和FHIT基因甲基化与蛋白表达的关系。[方法]应用甲基化特异性聚合酶链反应方法,对44例癌前病变、14例原位癌、37例浸润癌和10例慢性食管炎共105例患者组织DNA进行了p16和FHIT基因甲基化检测,应用免疫组织化学的方法检测了相应组织两基因蛋白表达情况,并进行相关性分析。[结果]在105例患者组织中,随着病变程度的加重,p16和FHIT基因甲基化频率和蛋白缺失率均呈逐渐增加的趋势,重度不典型增生、鳞状细胞原位癌及浸润癌的甲基化频率和蛋白表达缺失率均显著高于黏膜慢性炎症组,且p16和FHIT基因甲基化与蛋白失表达密切相关。[结论]p16和FHIT蛋白表达缺失是食管癌以及癌前病变发生的一个早期事件;p16和FHIT基因可能通过启动子区甲基化失活参与了食管癌的发生发展过程。

[ Objective] To study the relationship of p16 and FHIT methylafion with the protein expression in the esophageal carcinogenesis. [Methods] Methylated-specifie PCR （MSP） was performed to detect the p16 and FHIT methylfion status in 44 eases of esophageal preeancerous lesions, 14 carcinoma in situ （CIS）, 37 infiltrated carcinoma and 10 chronic esophatitis （CE）. Loss of protein expression of p16 and FHIT was detected immunohistochemically and the relationship of methylation and loss of protein expression was evaluated with correlation analysis. [Results] Among 105 cases, the methylation frequencies and loss of protein expression of both genes were showed to be increasing tendency with the aggravation of the disease. The methylation frequencies and loss of protein expression of p16 and FHIT in the severe dysplasia, CIS and infiltrated carcinoma groups were apparendy higher than that in the CE. The methylation status of p16 and FHIT showed signifieandy association with the expression of proteinum. [Conclusion] Loss of protein expression of p16 and FHIT is an early event in the esophageal carcinogenesis. Inactivation of p16 and FHIT might play an important role in the progression of esophageal eaneer by promoting the inaetivation of methylation.