title: CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients.
abstract: Cervical cancer is the principal cause of death due to cancer in women. Five-year survival rate ranges from 15-80%, depending on the extent of the disease. New predictive markers for relapse may increase survival rates by improving treatment of patients at high risk for relapse. The gene products of CDH1 and CDH13, namely E-cadherin and H-cadherin, play a key role in cell-cell adhesion. Inactivation of the cadherin-mediated cell adhesion system, caused by aberrant methylation, is a common finding in human cancers. To test the hypothesis that CDH1/CDH13 methylation is a prognostic marker in cervical cancer we determined the methylation status of CDH1/CDH13 in serum samples from 93 cervical cancer patients. Methylation analysis was carried out using MethyLight. Aberrant methylation of the 5'-region of CDH1 or CDH13 was observed in 43% (40 of 93) of the patients. Cervical cancer patients with unmethylated CDH1/CDH13 in serum samples showed significantly better disease-free survival in univariate and multivariate analysis. Median disease-free survival for CDH1/CDH13 methylation negative and positive patients was 4.3 years and 1.2 years, respectively. Our results suggest that detection of aberrant methylation of CDH1/CDH13 may be of potential use as a marker for selecting cervical cancer patients at high risk for relapse who could benefit from additional systemic therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck University Hospital, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Widschwendter
authors.forename: Lennart
authors.initials: L
authors.lastname: Ivarsson
authors.forename: Anya
authors.initials: A
authors.lastname: Blassnig
authors.forename: Hannes M
authors.initials: HM
authors.lastname: Müller
authors.forename: Heidi
authors.initials: H
authors.lastname: Fiegl
authors.forename: Annemarie
authors.initials: A
authors.lastname: Wiedemair
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Müller-Holzner
authors.forename: Georg
authors.initials: G
authors.lastname: Goebel
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Martin
authors.initials: M
authors.lastname: Widschwendter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000097:blood / Q000235:genetics*; D018196:Carcinoma, Adenosquamous / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D004273:DNA, Neoplasm; C099972:H-cadherin