2002 CTOS Annual Meeting Posters — Pathology

CELL CYCLE ABNORMALITIES IN GIANT CELL TUMORS
[Abstract ID: 32]

Category: Pathology

Authors: Adel Kauzman¹, Shu Qiu Li¹, Grace Bradley¹, Robert Bell¹, Jay Wunder¹, Joel Werier¹, Rita Kandel¹

Author Institutions: ¹Mount Sinai Hospital, Ontario, Canada

Presenter: Rita Kandel
rkandel@mtsinai.on.ca

Correspondent: Rita Kandel
rkandel@mtsinai.on.ca
Toronto Ontario Canada M5G 1G5
Ph: 416-586-8516
Fax: 416-586-8628

Objectives: Objective: Since alterations in cell cycle proteins have been implicated in the pathogenesis of human tumors, GCTs were examined for changes in cyclin D1, which is necessary for the G1/S and cyclin B1, which is essential for the G2/M transition points of the cell cycle. In addition, proliferative activity was assessed.

Methods: Methods: Formalin-fixed, paraffin-embedded, nondecalcified tissue sections from 32 cases of GCT were examined by light microscopy after H&E staining and following immunostaining with antibodies reactive with cyclin D1, cyclin B1, and Ki-67. Immunopositivity in 5% of cells was considered indicative of overexpression. DNA was extracted and cyclin D1 gene status was determined using semiquantitative differential PCR and densitometry. Amplification was defined as 3 standard deviations above the mean ratio of the negative control.

Results: Results: Histologically, the tumors had areas composed of mononuclear cells with interspersed multinucleated giant cells. DNA could be extracted and amplified from 31 of 32 cases. Cyclin D1 gene amplification was observed in 19 of the 31 cases (61%). All tumors showed cyclin D1 and B1, and Ki-67 staining. Cyclin D1 expression was seen predominantly in the multinucleated giant cells and only occasional mononuclear cells were positive. Cyclin B1 and Ki-67 staining occurred only in the mononuclear cells.

Conclusions: Conclusions: Cyclin D1 was altered in GCTs as 61% of cases showed gene amplification and 100% showed protein overexpression in giant cells. Mononuclear cells were the proliferating cells as they showed MIB-1 and cyclin B1 staining. It is possible that cyclin D1 dysregulation contributes to giant cell formation.