Xu Jun, Wang Hong-Lin, Lu Gao-Chuan, Wang Zhi-Jie, Lin Xiao, Zhou Hong-Wei
Department of Obstetrics and Gynecology, Eighth People's Hospital of Shanghai, Shanghai 200233, China.
Zhonghua Fu Chan Ke Za Zhi. 2007 Jun;42(6):394-7.
To investigate the change of aberrant methylation of p16, CDH, RASSF1A and TIMP3 in cervical carcinoma and their significance in cervical carcinoma.
Using the bisulfite-modification technique and methylation-specific PCR (MSP), we examined the aberrant promoter hypermethylation patterns of 4 tumor suppressor genes (p16, CDH1, RASSF1A, TIMP3) in 140 samples of cervical intraepithelial neoplasia (CINI, n = 40), CINII-III (n = 40), cervical carcinomas (CC, n = 40), and normal cervical tissue as a control group (n = 20).
(1) Methylation was completely absent in control tissues. (2) Significant differences between CINII-III group and CINI 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% vs 2%, 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 CINII-III group, but with no significant differences (P > 0.05). (4) Significant differences between CC and CINIfor 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 CINII-III 55% (22/40; P < 0.05). In comparison between CINI8% (3/40) and CC and CINII-III, these figures were significantly different (P < 0.05).
Among the four genes, p16, 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.
探讨宫颈癌中p16、CDH、RASSF1A和TIMP3基因异常甲基化的变化及其在宫颈癌中的意义。
采用亚硫酸氢盐修饰技术和甲基化特异性PCR（MSP），检测140例宫颈上皮内瘤变（CINI，n = 40）、CINII - III（n = 40）、宫颈癌（CC，n = 40）及正常宫颈组织（对照组，n = 20）中4个抑癌基因（p16、CDH1、RASSF1A、TIMP3）启动子的异常高甲基化模式。
（1）对照组组织中未检测到甲基化。（2）CINII - III组与CINI组在p16和CDH1基因甲基化水平上存在显著差异（22% vs 2%，P < 0.05；35% vs 5%，P < 0.05），而RASSF1A和TIMP3基因在两组间无显著差异（12% vs 2%，P > 0.05；15% vs 2%，P > 0.05）。（3）宫颈癌组中p16（40%）、CDH1（58%）、RASSF1A（20%）和TIMP3（35%）的甲基化水平高于相应的CINII - III组，但差异无统计学意义（P > 0.05）。（4）宫颈癌组与CINI组在p16、CDH1、RASSF1A和TIMP3基因甲基化水平上存在显著差异（P < 0.05）。（5）至少一个基因发生甲基化较为常见。宫颈癌组中这一比例为90%（36/40），与CINII - III组的55%（22/40）相比，差异有统计学意义（P < 0.05）。CINI组中这一比例为8%（3/40），与宫颈癌组及CINII - III组相比，差异有统计学意义（P < 0.05）。
在p16、CDH、RASSF1A和TIMP3这四个基因中，随着组织病理学变化程度的增加，甲基化水平有显著升高的趋势。这表明抑癌基因的异常甲基化在宫颈癌发生发展过程中起作用。这可能有助于识别宫颈癌发生风险增加或病情发展及进展的女性。
