title: Promoter methylation and downregulated expression of theTBX15gene in ovarian carcinoma.
abstract: TBX15is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of theTBX15gene promoter and the expression levels ofTBX15in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role ofTBX15in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues).TBX15promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype.
authors.affiliation: Pathological Anatomy Unit, Department of Life Sciences, University of Modena and Reggio Emilia, I-41124 Modena, Italy; University Institute of Pathology, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Gaia
authors.initials: G
authors.lastname: Gozzi
authors.affiliation: University Institute of Pathology, Lausanne University Hospital, 1011 Lausanne, Switzerland; Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Sonia T
authors.initials: ST
authors.lastname: Chelbi
authors.affiliation: Pathological Anatomy Unit, Department of Life Sciences, University of Modena and Reggio Emilia, I-41124 Modena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Manni
authors.affiliation: University Institute of Pathology, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Loredana
authors.initials: L
authors.lastname: Alberti
authors.affiliation: Pathological Anatomy Unit, Department of Life Sciences, University of Modena and Reggio Emilia, I-41124 Modena, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Fonda
authors.affiliation: Pathological Anatomy Unit, Department of Life Sciences, University of Modena and Reggio Emilia, I-41124 Modena, Italy; University Institute of Pathology, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Saponaro
authors.affiliation: Department of Diagnostic Medicine, Clinic and Public Health, University of Modena and Reggio Emilia, I-41124 Modena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Fabbiani
authors.affiliation: Department of Diagnostic Medicine, Clinic and Public Health, University of Modena and Reggio Emilia, I-41124 Modena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rivasi
authors.affiliation: University Institute of Pathology, Lausanne University Hospital, 1011 Lausanne, Switzerland; Biopath Lab, Medical Biology and Pathology, 1006 Lausanne, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Benhattar
authors.affiliation: Pathological Anatomy Unit, Department of Life Sciences, University of Modena and Reggio Emilia, I-41124 Modena, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Losi
keywords: DNA methylation; TBX15; epigenetics; immunohistochemistry; ovarian carcinoma; pyrosequencing