title: Secondary malignant giant-cell tumour of bone: molecular abnormalities of p53 and H-ras gene correlated with malignant transformation.
abstract: OBJECTIVE
  We report two cases of secondary malignant giant-cell tumour occurring without irradiation therapy. To elucidate the mechanism of malignant transformation in this tumour, we searched for the molecular abnormalities of p53, MDM2 and the H-ras genes.
  
  
  RESULTS
  These cases were retrieved after a review of 103 cases of primary giant-cell tumour of bone, registered in our institute. One case occurred in the distal femur of a 42-year-old female after surgical curettage, while the other arose in the acetabulum of a 25-year-old male after en bloc resection. Microscopically, the malignant tumour in the distal femur was composed of a proliferation of ovoid or fusiform cells arranged in fascicles with high mitotic activities. The malignant transformed tumour in the acetabulum was made up of pleomorphic tumour cells with atypical mitoses. In the tumour of the distal femur, both p53 and H-ras mutations were detected. Abnormal nuclear accumulation of p53 protein and c-myc expression were also revealed by immunohistochemistry. In both cases, the recurrent malignant tumour over-expressed MMP-9 and revealed a higher MIB-1-labelling index compared with the primary conventional giant-cell tumour.
  
  
  CONCLUSIONS
  Our results suggest that multiple oncogene or tumour suppressor gene mutations may play an important role during malignant transformation in conventional giant-cell tumours.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Oda
authors.forename: A
authors.initials: A
authors.lastname: Sakamoto
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: M
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D000328:Adult; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D005260:Female; D005870:Giant Cell Tumors / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009154:Mutation; D020125:Mutation, Missense; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D018631:ras Proteins / Q000032:analysis / Q000235:genetics
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D020780:Matrix Metalloproteinase 9; D018631:ras Proteins