Hypermethylation of selected genes in endometrial carcinogenesis.
OBJECTIVE
Endometrial cancer is one of the most common malignancies in women. The prevention has failed so far to develop an effective screening program and its incidence is rising in proportion to the incidence of cervical cancer. In recent years the investigation of malignancy genomics (genetic and epigenetic changes) has become the main focus of scientists because of its high sensitivity and specificity.


METHODS
We conducted a prospective longitudinal study at the Dpt. of Gynaecology and Obstetrics of the Jessenius Faculty of Medicine in Martin from 2010 to 2012, in collaboration with the Institute of Pathology of the University Hospital in Martin. We analysed paraffin blocks of endometrial tissue from 123 women with endometrial cancer, hyperplasia and normal endometrial findings. By the use of bisulphidic modification technique and nested methylation-specific PCR (MSP), we analysed the methylation patterns of three genes: GSTP1, E-cad, RASSF1.


RESULTS
We found a statistically significant increase of methylation of the RASSF1 gene in endometrial cancer compared to simplex hyperplasia and intact endometrial tissue (p<0.001). GSTP1 and E-cad did not show any relevant methylation pattern in various endometrial lesions.


CONCLUSIONS
According to the results of our study, RASSF1 gene methylation could serve as a prognostic factor of endometrial carcinogenesis and could help to predict the behaviour of endometrial hyperplasia.
Department of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, University Hospital Martin, Slovakia. visnovsky@jfmed.uniba.sk.
Jozef
J
Visnovsky
Department of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, University Hospital Martin, Slovakia.
Roman
R
Fiolka
Department of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, University Hospital Martin, Slovakia.
Erik
E
Kudela
Department of Pathologic Anatomy, Jessenius Faculty of Medicine, University Hospital Martin, Slovakia.
Pavol
P
Slavik
Department of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, University Hospital Martin, Slovakia.
Milan
M
Krkoska
Institute of Molecular Biology, Jessenius Faculty of Medicine, Martin, Slovakia.
Zora
Z
Lasabová
Department of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, University Hospital Martin, Slovakia.
Jan
J
Danko
D000328:Adult; D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004717:Endometrium / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia / Q000453:epidemiology / Q000235:genetics; D015994:Incidence; D008137:Longitudinal Studies; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi