title: Central giant cell lesion of the jaws: study of CCND1 gene amplification and p16INK4a protein levels.
abstract: Central giant cell lesions (CGCLs) are uncommon benign jaw lesions with uncertain etiology and a variable clinical behavior. In neoplasms, alterations in molecules involved in the G1/S checkpoint are frequently found. Loss of p16(INK4a) expression or overexpression of cyclin D1 may stimulate cell proliferation. The purpose of this study was to analyze CCND1 gene amplification and the expression of p16(INK4a) in CGCLs. Structural analysis of the CCND1 was performed using chromogenic in situ hybridization. Immmunohistochemistry was used to identify p16(INK4a) protein levels. Statistical analysis correlated the two biomarkers with clinical behavior and between each other. Twenty-four lesions were included, being 11 aggressive and 13 non-aggressive. Moderate/high-level CCND1 amplification was found in 12 lesions. Also, immunoreactivity for p16(INK4a) was present in 12 cases, mainly in mononuclear cells. There was a significantly higher level of p16(INK4a) expression in mononuclear cells of non-aggressive lesions and lesions with moderate/high-level CCND1 amplification in mononuclear cells. It could be speculated that some CGCLs may develop as a true benign neoplasm. The higher expression of p16(INK4a) in non-aggressive lesions and in cases with moderate/high-level CCND1 amplification may show that these molecules have a role in CGCLs.
authors.affiliation: Department of Dental Clinic, Discipline of Oral and Maxillofacial Surgery and Stomatology, Federal University of Ceara School of Dentistry, Fortaleza, Brazil.
authors.forename: Renato Luiz Maia
authors.initials: RL
authors.lastname: Nogueira
authors.forename: Mário Henrique Girão
authors.initials: MH
authors.lastname: Faria
authors.forename: Rafael Lima Verde
authors.initials: RL
authors.lastname: Osterne
authors.forename: Roberta Barroso
authors.initials: RB
authors.lastname: Cavalcante
authors.forename: Ronaldo Albuquerque
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Cassiano Francisco Weege
authors.initials: CF
authors.lastname: Nonaka
authors.forename: Silvia Helena Barem
authors.initials: SH
authors.lastname: Rabenhorst
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D019938:Cyclin D1 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015870:Gene Expression; D015726:Giant Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007568:Jaw / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: C530104:CCND1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019938:Cyclin D1