乳腺癌和乳腺导管内增生性病变Notch1基因甲基化的检测及临床意义

目的 探讨Notch1基因甲基化与乳腺浸润性导管癌(IDC)及乳腺导管内增生性病变的相关性.方法 用基质辅助激光解析电离时间飞行质谱仪(MALDI-TOF MS)对89例乳腺IDC、20例导管原位癌(DCLS)、11例不典型导管增生(ADH)及20例普通型导管增生(UDH)组织进行Notch1基因甲基化的定量检测.采用...

Detection and clinical significance of Notch1 methylation in breast cancer and intraductal proliferative breast lesions

Objective To explore the relevance between the promoter methylation status of Notch1gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast.Methods Methylation status of Notch1 gene in human breast invasive ductal carcinoma(IDC,n=89),ductal carcinoma in situ (DOS,n=20),atypical ductal hyperplasia(ADH,,n=11)and usual ductal hyperplasia(UDH,n=20)were quantitatively evaluated by MALDI-TOF MS.The expression of Notch1 protein was detected by immunohistochemical stain(SP method).Results Positive expression rates of Notch1 protein in IDC and DCIS were 91.0%(81/89)and 75.0%(15/20),respectively,which were significandy higller than those 0f ADH(4/11)and UDH(30.0%.6/20;P＜0.05).Notch1 protein expression was correlated significantly with lymph node metastasis,pathological grades and TNM stages of IDC.The mean methylation levels of Notch1 gene at CpG_3,CpC 4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS.ADH and UDH groups(P＜0.0083).In breast carcinomas, the mean methylation rates of Notch1 gene at CpG-4.5,CpG-10.11,and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis(P＜0.05):and the methylation rates at CpG_14.15.16 and CpG_18 lociin stage Ⅰ were lower than that in stage Ⅱ,further lower than that in stage Ⅲ(P＜0.05);and that in CpG_1.2,CpG_12.13 loci in grade Ⅰ(highly-differentiated group)were higher than that in grade Ⅱ(moderate-differentiated group)and grade Ⅲ(peody-differentiated group) (P＜0.05);and the methylation rates at CpG_3,CpG_8 and CpG_14.15.16 loci in ER+ PR+ HER2-group were lower than that in ER-PR-HER2+ group(P＜0.05).Conclusions There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notehl protein.This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1,and this change may have important significance in breast tumorigenesis and the development.Specific hypomethylation at CpG_3,CpG_4.5 and CpG_8 loci of Notehl gene may play a role in the pathogenesis of breast carcinoma,suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.