食管癌前病变组织p16及FHIT基因甲基化探讨

目的:探讨食管癌前病变组织p16及FHIT基因启动子区CpG岛的甲基化状况.方法:采用甲基化特异性聚合酶链反应(MSP)方法,对食管癌前病变不同阶段及鳞状细胞原位癌的病变组织进行了甲基化检测,并与同一个体相应的病变旁组织及慢性食管炎和浸润性鳞癌组织的甲基化情况进行了时比分析研究.结果:轻度、中重度不典型增生、鳞状细胞原位癌和浸润癌共95例病变组织中p16基因的甲基化频率分别为22.73%、59.09%、78.57%、64.86%:FHIT基因的甲基化频率分别为22.73%、45.45%、64.29%、67.57%.同一个体相应的95例病变旁对照组织中16例未检测成功,余79例中5例(6.33%)p16基因甲基化,3例(3.80%)FHIT基因甲基化,与病变组织相比,均有统计学差异.10例慢性食管炎组织中1例p16基因甲基化,未发现FHIT基因甲基化.结论:p16及FHIT基因甲基化在癌前病变阶段就已经存在,可能是食管癌发生的早期事件之一.

CpG Island Methylation of p16 and FHIT Gene in Tissues of the Esophageal Precancerous Lesions

Objective: To detect aberrant CpG island methylation of promoter of the p16 and FHIT gene in tissues of esophageal precancerous lesions. Methods: Specific methylation-specific PCR (MSP) was used to detect CpG island methylation status of the p16 and FHIT gene in esophageal precancerous lesions, carcinoma in situ (CIS) and infiltrated carcinoma of esophageal squamous cell, and comparison analysis was performed in their corresponding nonmalignant tissues adjacent to the lesions and chronic esophagitis. Results: In total 95 esophageal lesions, the frequency of the p16 methylaion in mild, moderate and severe atypical hyperplasia, CIS and infiltrated carcinoma of esophageal squamous cell was 22.73%, 59.09%, 78.57% and 64.86%, and the frequency of the FHIT methylaion was 22.73%, 45.45%, 64.29% and 67.57%, respectively. Whereas in the 95 cases with corresponding non-cancerous tissues of the esophageal lesions, 16 were not detected successfully, and in the other 79 cases, five of the 79 cases (6.33%) in p16 and three (3.80%) in FHIT were found to be methylated. The significant difference in methylation of both genes between the various stages of lesions and the corresponding nonmalignant tissues was observed (P=0.000). In 10 chronic esophagitis, 1 (10%) was found p16 methylaion and none FHIT methylation was found. Conclusion: P16 and FHIT methylaion exist in the esophageal precancerous lesions, and it might be one of the early events in the occurrence of esophageal carcinoma.