Aberrant DNA hypermethylation of hMLH-1 and CDKN2A/p16 genes in benign, premalignant and malignant endometrial lesions.
OBJECTIVE
aberrant gene function and transcriptional silencing by CpG island hypermethylation have become a critical component in the initiation and progression of endometrial cancer. The aim of this study was to investigate the methylation status of genes associated with aberrant DNA hypermethylation in benign, premalignant and malignant endometrial lesions.


METHODS
using nested methylation-specific PCR, we assessed the methylation of the promoter regions of two genes, hMLH1 and CDKN2A/p16, in tissue samples from endometrial polyps (EP), atypical hyperplasia (AH) and endometrial cancer (EC).


RESULTS
the promoter region of at least one of the two genes was aberrantly methylated in EP (hMLH1 42%, CDKN2A/p16 16%), AH (hMLH1 16%, CDKN2A/p16 50%), EC (hMLH1 50%, CDKN2A/p16 75%). Interestingly, hypermethylation of both genes was found with significant increased frequence in AH and EC, but not in benign lesions.


CONCLUSIONS
our preliminary findings seem to suggest that the association of the two genes hMLH1 and CDKN2A/p16 may allow a differential diagnosis between benign and premalignant/malignant endometrial lesions; this further supports the hypothesis that methylation of such DNA mismatch repair and tumour-suppressor genes may be associated with endometrial carcinogenesis thus representing a valuable target for selective pharmacologic therapy.
Guida
M
M
Department of Gynaecology and Obstetrics, University of Naples "Federico II", Italy.
Sanguedolce
F
F
Bufo
P
P
Di Spiezio Sardo
A
A
Bifulco
G
G
Nappi
C
C
Pannone
G
G
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011127:Polyps / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014591:Uterine Diseases / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D019941:Cyclin-Dependent Kinase Inhibitor p16; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1