Frequent Upregulation of Cyclin D1 and p16INK4a Expression with Low Ki-67 Scores in Multinucleated Giant Cells

Abstract

Background/Aims: 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. Conclusion: 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.