[Clinical significance of detection of tumor suppressor genes aberrant methylation in cervical carcinoma tissue].
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, 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).


RESULTS
(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).


CONCLUSIONS
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.
Xu
Jun
J
Department of Obstetrics and Gynecology, Eighth People's Hospital of Shanghai, Shanghai 200233, China.
Wang
Hong-Lin
HL
Lu
Gao-Chuan
GC
Wang
Zhi-Jie
ZJ
Lin
Xiao
X
Zhou
Hong-Wei
HW
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; C411762:RASSF1 protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D025521:Tumor Suppressor Proteins