血浆p16和FHIT基因甲基化在食管癌及癌前病变检测的临床意义

目的:研究食管癌及癌前病变患者血浆中p16和FHIT基因甲基化情况,探讨其对食管早期癌和癌前病变诊断的临床应用价值。方法:应用甲基化特异性聚合酶链反应(methylation-specific PCR,MSP)方法,对食管癌及癌前病变、慢性食管炎患者组织及血浆标本进行了p16和FHIT基因甲基化检测。结果:在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中,分别发现18例、11例、24例和1例p16基因甲基化,15例、9例、25例和0例FHIT基因甲基化。癌前病变和慢性食管炎患者血浆中未发现两基因甲基化。51例食管癌患者血浆中共检出14例p16基因和16例FHIT基因甲基化,其中2例为原位癌。结论:p16及FHIT基因甲基化检测有望将食管癌的筛查提前到原位癌阶段,为食管癌的早期发现提供帮助。

Clinical significance of methylation of p16 and FHIT genes in esophageal carcinoma and precancerous diseases

Objective:To detect aberrant CpG island methylation of the p16 and fragile histidine triad(FHIT) genes in tumor tissues and plasma of patients with esophageal carcinoma and precancerous diseases and to evaluate their clinicopathological and prognostic significance.Methods:Methylation-specific PCR(MSP) was used to detect CpG island methylation statuses of the p16 and FHIT genes in the tumor tissues and plasma of patients with esophageal squamous cell carcinoma(ESCC),esophageal precancerous conditions(EPC),and chronic esophagitis(CE).Results: Totally 105 patients were tested in this study.The p16 gene methylation was detected in 18 out of 44 specimens of EPC,11 out of 14 specimens of carcinoma in situ (CIS),24 out of 37 specimens of infiltrated cancer,and 1 out of 10 specimens of CE,respectively.FHIT gene methylation was observed in 15 specimens of EPC,9 specimens of CIS,25 specimens of infiltrated cancer,and 0 specimens of CE,respectively.However,p16 and FHIT methylation was not found in the plasma of patients with EPC and CE.In the plasma of 51 patients with ESCC,p16 gene methylation was detected in 14 patients and FHIT gene methylation was found in 16 patients.Among them,2 patients had CIS.Conclusion:The detection of p16 and FHIT gene methylation might advance the screening of esophageal carcinoma to the CIS stage,which was useful to detect ESCC in the early stage.