Immunohistochemical expression of p53, MDM2, Ki‐67 and PCNA in central giant cell granuloma and giant cell tumor

Abstract

Central gaint cell granuloma (CGCG) is a reactive bone lesion that occurs mainly in the jaws. The gaint cell tumour (GCT) is a benign locally aggressive neoplasm located near the articular end of tubular bones. Both lesions are characterised histologically by multinucleated gaint cells in a background of ovoid to spindle‐shaped mesenchymal cells. There is a basic question whether both lesions are separate entities or variants of the same disease. The study of cell cycle‐associated proteins may give insights into clarifing such question. The expression of these protiens is also important to determine the cell cycle regulation in both tumours. The purpose of this study was to evaluate the immunohistochimical expression of p53, MDM2, Ki‐67 and PCNA in CGCG and GCT. The results demonstrated that, despite the lack of p53 immunoreactivity, all the samples showed wide expression of MDM2. The percentage of Ki‐67‐and PCNA‐positive cell in CGCG was statistically higher than that of GCT. Our findings shwo that CGCG has a higher proliferative activity compared with that of the GCT. Our results also suggest that p53 inactivation by MDM2 expression may be involved in the pathogenesis of gaint cell lesions of the jaws and long bones.

Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone

“…These metastatic tumours show less expression of the proliferation marker Ki-67 than continuous slow-growing and rapidly growing metastases. Other studies, however, have reported no consistent difference in the mitotic index [1,2,15] or in expression of proliferation and other tumour markers in primary and recurrent GCTBs associated with lung metastasis [21][22][23][24][25]. We noted that the immunophenotype of giant cells in primary (non-metastatic and metastatic) GCTBs and lung nodules was identical, indicating that the osteoclasts are essentially reactive cells recruited by receptor activator of nuclear factor-κB ligandexpressing mononuclear stromal cells [13]; the role of osteoclast specific proteases, such as cathepsin K [26], in lung nodule formation has not been determined, but it would be expected that this enzyme would be similarly expressed by osteoclasts in primary and secondary GCTBs.…”

Significance of β-catenin expression for the incidence of pathological fractures in giant cell tumors of bone

“…Individual genes included in the Wnt pathway influence the destructivity of GCTB and promote cell growth. It is widely known that b-catenin has an important role in the Wnt signaling pathway, as well as in the incidence of numerous primary mesenchymal tumors of bone and soft tissue [11,12,13,14].…”

Centrosome abnormalities in giant cell tumour of bone: possible association with chromosomal instability

“…4 TP53 overexpression as an indicator of TP53 mutation has been correlated with lung metastasis and recurrence of giant cell tumour of bone according to some but not all observers. [18][19][20] The cell-cycle regulator protein, CCND1, together with CDKN1A, both of which have a regulatory role in centrosome reduplication, has also been reported to be overexpressed in the giant cell component of giant cell tumour of bone. [21][22] A possible role of the oncogene MYCC has also been suggested in the pathogenesis of this tumour by Gamberi et al, 23 who found that MYCC was overexpressed in both the giant cell and mononuclear cell populations of metastatic cases of giant cell tumour of bones.…”