title: Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix.
abstract: Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors.
authors.affiliation: Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.|Cancer Immunomodulation Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.|Division of Infection and Immunity, Rayne Institute, University College London (UCL), London, UK.
authors.forename: Idoia
authors.initials: I
authors.lastname: Blanco-Luquin
authors.affiliation: Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.|Department of Pathology, Complejo Hospitalario de Navarra, Navarra Health Service, Pamplona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Guarch
authors.affiliation: Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Ojer
authors.affiliation: Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.|Division of Infection and Immunity, Rayne Institute, University College London (UCL), London, UK.
authors.forename: Noemí
authors.initials: N
authors.lastname: Pérez-Janices
authors.affiliation: Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Martín-Sánchez
authors.affiliation: Department of Pathology, Complejo Hospitalario de Navarra, Navarra Health Service, Pamplona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Maria-Ruiz
authors.affiliation: Genomics Unit, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Monreal-Santesteban
authors.affiliation: Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Blanco-Fernandez
authors.affiliation: Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pernaut-Leza
authors.affiliation: Cancer Immunomodulation Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.|Division of Infection and Immunity, Rayne Institute, University College London (UCL), London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Escors
authors.affiliation: Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.|Genomics Unit, Navarrabiomed-Fundación Miguel Servet, Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Guerrero-Setas
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics; D002584:Cervix Uteri / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C403514:CADM1 protein, human; C000614131:CDKN2A protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D019941:Cyclin-Dependent Kinase Inhibitor p16; D007136:Immunoglobulins; D009363:Neoplasm Proteins; C411762:RASSF1 protein, human; C481348:SPZ1 protein, human; D025521:Tumor Suppressor Proteins
keywords: adenocarcinoma; methylation; prognosis; squamous cervical cancer