title: Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.
abstract: Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.
authors.affiliation: 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Panagopoulou
authors.affiliation: 2 Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Lambropoulou
authors.affiliation: 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.|3 Department of Oncology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Balgkouranidou
authors.affiliation: 4 Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Nena
authors.affiliation: 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Makrina
authors.initials: M
authors.lastname: Karaglani
authors.affiliation: 2 Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Nicolaidou
authors.affiliation: 5 Fourth University Clinic of Obstetrics and Gynecology, Hippokrateion Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Anthi
authors.initials: A
authors.lastname: Asimaki
authors.affiliation: 4 Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Theocharis
authors.initials: T
authors.lastname: Konstantinidis
authors.affiliation: 4 Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Theodoros C
authors.initials: TC
authors.lastname: Constantinidis
authors.affiliation: 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Kolios
authors.affiliation: 3 Department of Oncology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kakolyris
authors.affiliation: 5 Fourth University Clinic of Obstetrics and Gynecology, Hippokrateion Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Agorastos
authors.affiliation: 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Chatzaki
mesh_terms: D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics*; D012306:Risk; D002583:Uterine Cervical Neoplasms / Q000209:etiology*; D002578:Uterine Cervical Dysplasia / Q000209:etiology
chemical_list: C410024:BRMS1 protein, human; D012097:Repressor Proteins
keywords: BRMS1; Methylation; cancer; epigenetic; human papilloma virus; uterine cervix