子宫颈癌组织中抑癌基因DNA甲基化的检测  

Clinical significance of detection of tumor suppressor genes aberrant methylation in cervical carcinoma tissue

作　　者：徐军[1] 王红琳[1] 陆杲川[1] 王治洁[1] 林晓[1] 周宏卫 

机构地区：[1]上海市第八人民医院妇产科,200233

出　　处：《中华妇产科杂志》2007年第6期394-397,共4页Chinese Journal of Obstetrics and Gynecology

基　　金：上海市科学技术委员会科研计划项目课题(044119733)

摘　　要：目的通过分析宫颈上皮内瘤变(CIN)和宫颈癌组织中 p16、CDH1、RASSF1A和TIMP3基因 DNA 甲基化的变化情况,探讨其在宫颈癌发生中的意义。方法用甲基化特异性聚合酶链反应技术(MSP)对 CIN Ⅰ组(40份)、CIN Ⅱ～Ⅲ组(40份)、宫颈癌组(40份)病变组织中 p16、CDH1、RASSF1A 和 TIMP3基因 DNA 甲基化程度进行检测。另取正常宫颈组织20份作为对照组。结果 (1)对照组中 p16、CDH1、RASSF1A 和 TIMP3基因的 DNA 甲基化阳性率均为0。(2)p16和CDH1基因的 DNA 甲基化阳性率,CINⅡ～Ⅲ组(分别为22%、35%)明显高于 CIN Ⅰ组(分别为2%、5%,P<0.05);RASSF1A 和 TIMP3基因的 DNA 甲基化阳性率,CINⅡ～Ⅲ组(分别为12%、15%)虽高于 CIN Ⅰ组(均为2%),但差异无统计学意义(P>0.05)。(3)宫颈癌组 p16(40%)、CDH1(58%)、RASSF1A(20%)和 TIMP3(35%)基因的 DNA 甲基化阳性率虽均高于CINⅡ～Ⅲ组,但差异无统计学意义(P>0.05)。(4)宫颈癌组 p16、CDH1、RASSF1A 和 TIMP3基因的 DNA 甲基化阳性率均高于CIN Ⅰ组,差异有统计学意义(P<0.05)。(5)上述基因的 DNA 甲基化的总阳性率(即任何一个基因出现甲基化即为阳性),宫颈癌组(90%)明显高于 CINⅡ～Ⅲ组(55%,P<0.05),且此两组均明显高于 CIN Ⅰ组(8%,P<0.05)。结论随着从宫颈不典型增生向浸润癌的进展,p16、CDH1、RASSF1A和 TIMP3基因的 DNA 甲基化阳性率明显升高,提示抑癌基因的 DNA 甲基化在宫颈癌发生、发展中起着一定作用,可能成为判断宫颈癌发生、发展的重要指标。Objective To investigate the change of aberrant methylation of p16, CDH, RASSF1A and TIMP3 in cervical carcinoma and their significance in cervical carcinoma. Methods Using the bisulfite-modification technique and methylation-specific PCR （MSP）, we examined the aberrant promoter hypermethylation patterns of 4 tumor suppressor genes （p16, CDH1, RASSF1 A, TIMP3 ） in 140 samples of cervical intraepithelial neoplasia （ CIN Ⅰ , n = 40 ）, CIN Ⅱ- Ⅲ（ n = 40 ）, cervical carcinomas （ CC, n = 40 ）, and normal cervical tissue as a control group （n = 20）. Results （1）Methylation was completely absent in control tissues. （2）Significant differences between CIN Ⅱ-m group and CIN I group were detected for p16 and CDH1 （22% vs 2%, P 〈0. 05 ; 35% vs 5%, P 〈 0. 05）, while there were no significant differences between the two groups for RASSF1A and TIMP3（12% vs2% , P〉0.05; 15% vs 2% , P〉0.05）. （3） The presence of methylation of p16 （40%）, CDH1 （58%）, RASSF1A （20%） and TIMP3 （35%） in CC were higher than the corresponding CIN Ⅱ- m group, but with no significant differences （ P 〉 0. 05 ）. （ 4 ） Significant differences between CC and CIN I for p16, CDH1, RASSF1A and TIMP3 genes （P 〈 0. 05 ） were observed. （5）Methylation for at least one gene was a frequent event. These figures in CC 90% （36/ 40） were significantly different from CIN Ⅱ -Ⅲ 55% （22/40; P 〈0.05）. In comparison between CIN 1 8% （3/40） and CC and CIN Ⅱ- Ⅲ, these figures were significantly different （ P 〈 0. 05 ）. Conclusions Among the four genes, pl6,CDH,RASSF1A and TIMP3, there is a significant trend for increased methylation with increasing degree of histopathological change. It suggests that the aberrant methylation of tumor suppressor genes plays a role during cervical cancer development. This may help identify women at increased risk for or cancer development and progression.

关 键 词：宫颈肿瘤 宫颈上皮内瘤样病变 基因 肿瘤抑制 DNA甲基化 

分 类 号：R737.33[医药卫生—肿瘤]