[Hypermethylation of hMLH1 and microsatellite instability in ovarian mucinous tumors].
OBJECTIVE
To investigate the role of hMLH1 promoter hypermethylation and microsatellite instability (MSI) in the development of ovarian mucinous tumors.


METHODS
One hundred and seven of paraffin-embedded specimens of ovarian mucinous tumors (malignant 49, borderline 35, and benign 23) were collected from Women's Hospital, School of Medicine, Zhejiang University from 1995 to 2001. The assessment of MSI was based on the use of a panel of six microsatellite markers (BAT-25, BAT-26, BAT-40, D5S346, D17S250, and D2S123) by polymerase chain reaction (PCR). Hypermethylation of hMLH1 promoter region was detected using restriction cut analysis.


RESULTS
4.3% (1/23), 14.3% (5/35), and 36.7% (18/49) of benign tumors, borderline tumors, and malignant tumors respectively displayed hypermethylation of the hMLH1 promoter. The hMLH1 promoter hypermethylation rate of malignant group was significantly higher than that of borderline and benign group (P = 0.023, 0.004), but no significant difference between the borderline group and the benign group (P = 0.438); 4.3% (1/23), 8.6% (3/35), and 16.3% (8.49) of benign tumors, borderline tumors, and malignant tumors showed MSI positive phenotype. But there were no significant differences each other in the MSI positive phenotype rate; 75% (9/12) MSI positive phenotype ovarian mucinous tumors were hypermethylated at hMLH1 promoter, while the MSI-phenotype tumors were unmethylated in 84.2% (80.95) of cases. There was significant correlation between MSI positive phenotype and hMLH1 promoter hypermethylation (P = 0.000).


CONCLUSIONS
In ovarian mucinous tumors, malignant, borderline, and benign tumors exist hMLH1 promoter hypermethylation. Hypermethylation of hMLH1 promoter results MSI in ovarian mucinous tumors. Methylation of hMLH1 promoter and MSI may be involved in the carcinogenesis of ovarian mucinous cancer.
Chen
Huai-zeng
HZ
Department of Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
Ye
Da-feng
DF
Xie
Xing
X
Hu
Min
M
Lu
Wei-guo
WG
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D043171:Chromosomal Instability; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics*; D019175:DNA Methylation; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics; D004276:DNA, Satellite; D005260:Female; D052138:Genes, Neoplasm; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004276:DNA, Satellite; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1