Cyclin alterations in giant cell tumor of bone.
Cyclins play an important role in regulating the passage of dividing cells through critical checkpoints in the cell cycle. Because alterations of several cyclins, especially cyclin D1, have been implicated in the development of many human neoplasms, we examined 32 cases of giant cell tumor of long bones for cyclin D1 gene amplification and protein overexpression using differential polymerase chain reaction and immunohistochemistry, respectively. In addition, the expression of cyclin D3, cyclin B1, and the proliferation-associated antigen Ki-67 (MIB-1) was assessed immunohistochemically. Low-level cyclin D1 gene amplification was detected in 61% of giant cell tumor cases. All tumors showed cyclin D1, cyclin D3, cyclin B1, and Ki-67 (MIB-1) staining; however, the distribution was very characteristic. Cyclin D1 protein expression was seen predominantly in the nuclei of the giant cells, with occasional mononuclear cells staining. There was no correlation between cyclin D1 gene amplification and protein overexpression. Cyclin D3 staining showed a similar distribution, with 88% of cases showing protein overexpression. Cyclin D1 and/or D3 staining in the giant cells was never associated with staining for either cyclin B1 or Ki-67 (MIB-1), as the expression of the latter two proteins was restricted to the mononuclear cells. Cyclin B1 overexpression was seen in 44% of cases. Ki-67 (MIB-1) staining was present in all cases, and between 10 to 50% of the mononuclear cells were positive. These results suggest that alterations in cyclin D1 and/or D3 might play a role in the pathogenesis of giant cell tumor of bone.
Kauzman
Adel
A
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1x5, Canada.
Li
Shu Qiu
SQ
Bradley
Grace
G
Bell
Robert S
RS
Wunder
Jay S
JS
Kandel
Rita
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D019926:Cyclin B / Q000096:biosynthesis / Q000235:genetics; D056744:Cyclin B1; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D056743:Cyclin D3; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018212:Giant Cell Tumor of Bone / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C534699:CCNB1 protein, human; C534696:CCND3 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D056743:Cyclin D3; D016213:Cyclins; D019394:Ki-67 Antigen; D019938:Cyclin D1