title: Frequent upregulation of cyclin D1 and p16 expression with low Ki-67 scores in multinucleated giant cells.
abstract: OBJECTIVE
  Multinucleated giant cells are formed from the fusion of macrophages and are classified into foreign body-type giant cells (FBGCs), osteoclast-type giant cells (OCGCs) and Langhans-type giant cells (LHGCs). OCGCs display upregulated cyclin D1 expression with low Ki-67 activity. However, little is known about the expression of cell cycle regulators in the other types of multinucleated giant cells. We aimed to investigate the cell cycle status of multinucleated giant cells.
  
  
  METHODS
  The immunohistochemical expressions of cyclin D1, p16(INK4a) and Ki-67 were analyzed in a total of 127 cases showing multinucleated giant cells.
  
  
  RESULTS
  Cyclin D1 was overexpressed in 45 (88%) of 51 FBGC cases, 25 (86%) of 29 OCGC cases and 22 (47%) of 47 LHGC cases. p16(INK4a) showed diffuse nuclear and/or cytoplasmic overexpression in 45 (88%) of 51 FBGC cases, 27 (93%) of 29 OCGC cases and 24 (51%) of 47 LHGC cases. Ki-67 immunostaining was negative in almost all FBGC, OCGC and LHGC cases.
  
  
  CONCLUSIONS
  This study demonstrates that FBGCs and OCGCs frequently show upregulation of cyclin D1 and p16(INK4a) expression with low Ki-67 scores. This suggests that multinucleated giant cells are arrested in the G1/S cell cycle transition.
authors.affiliation: Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Choi
authors.forename: Ju-Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D002453:Cell Cycle; D019938:Cyclin D1 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints; D015726:Giant Cells / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D015743:Giant Cells, Foreign-Body / Q000378:metabolism / Q000473:pathology; D015744:Giant Cells, Langhans / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: C530104:CCND1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D019938:Cyclin D1