摘要目的 检测结直肠锯齿状病变中Wif-1基因启动子区甲基化状态及β连环蛋白的表达情况,探讨二者之间以及与结直肠锯齿状病变发生发展的关系.方法 收集增生性息肉52例、广基锯齿状腺瘤41例、传统锯齿状腺瘤23例,并取结直肠癌24例和24例正常结直肠黏膜组织作为对照进行β连环蛋白免疫组织化学染色,同时从上述各组中分别抽取增生性息肉29例、广基锯齿状腺瘤29例、传统锯齿状腺瘤19例、结直肠癌14例和正常结直肠黏膜组织16例进行SYBR Green PCR,检测Wif-1基因启动子区甲基化状态.结果 β连环蛋白异常阳性率在正常结直肠黏膜、增生性息肉、广基锯齿状腺瘤、传统锯齿状腺瘤及结直肠癌组中分别为12.5％ (3/24)、59.6％ (31/52)、63.4％(26/41)、73.9％(17/23)及100.0％(24/24),同时Wif-1基因启动子区甲基化率在以上各组中分别为2/16、10/29(34.5％)、16/29(55.2％)、15/19及13/14(P ＜0.05);传统锯齿状腺瘤中Wif-1基因甲基化与β连环蛋白表达呈正相关(r =0.536,P＜0.05).结论 β连环蛋白异常阳性率及Wif-1基因启动子区甲基化比例在锯齿状病变中明显升高,Wif-1基因启动子区甲基化可能是引起β连环蛋白异常表达的机制之一,二者通过Wnt/β连环蛋白信号通路异常激活可能参与锯齿状病变的发生发展过程.

abstractsObjective To investigate methylation status of Wif-1 and β-catenin expression in colorectal serrated lesions.Methods Various colorectal lesions were collected including 52 cases of hyperplastic polyps,41 cases of sessile serrated adenoma,23 cases of traditional serrated adenoma,24 cases of colorectal cancer and 24 cases of normal mucosa.All specimens were subject to immunohistochemical staining of β-catenin.SYBR Green PCR analysis of Wif-1 promoter methylation was performed in 29 cases of hyperplastic polyps,29 cases of sessile serrated adenoma,19 cases of traditional serrated adenoma,14 cases of colorectal cancer and 16 cases of normal mucosa.Results Abnormal expression rates of β-catenin in normal mucosa,hyperplastic polyps,sessile serrated adenoma,traditional serrated adenoma and colorectal cancer were 12.5％ (3/24),59.6％ (31/52),63.4％ (26/41),73.9％ (17/23) and 100.0％ (24/24),respectively.The corresponding methylation rates of Wif-1 promoter were 2/16,10/29 (34.5％),16/29 (55.2％),15/19 and 13/14 (P ＜ 0.05),respectively.Abnormal β-catenin expression was positively correlated with Wif-1 promoter methylation in traditional serrated adenomas (r =0.536,P ＜ 0.05).Conclusions Abnormal β-catenin expression and methylation rate of Wif-1 promoter are significantly higher in colorectal serrated lesions.Methylation of Wif-1 promoter may be related to the abnormal expression of β-catenin through activation of Wnt/β-catenin signaling pathway,which may contribute to the development of colorectal serrated lesions.