Molecular analysis of p53, MDM2 and H-ras genes in low-grade central osteosarcoma.
Low-grade central osteosarcoma is an uncommon form that is characterized by a long premorbid history, and is compatible with prolonged survival after treatment. However, molecular abnormalities are rare in low-grade central osteosarcomas, whereas p53 mutations occur in approximately 20% of conventional high-grade osteosarcomas. In this study, 21 cases of low-grade central osteosarcoma were analyzed for mutations of the p53 gene, amplification of the MDM2 gene, and mutations of the H-ras gene using formalin-fixed, paraffin-embedded materials. We also examined the expression of p53, MDM2, and p21WAF1 protein immunohistochemically and assessed the proliferation activities using the monoclonal antibody MIB-1. One case (4.7%) showed strong p53 immunoreactivity, whereas p53 gene mutations were not detected at all. Seven cases (33.3%) showed immunoreactivity for MDM2 protein. As for gene alterations, MDM2 amplification was found in four cases (19.0%). p21WAF1 expression was detected in 12 cases (57.1%). MIB-1-LI showed very low levels in all the cases and no significant correlation with p53 or MDM2 immuno-reactivity. None of the tumors showed H-ras mutations. In conclusion, the number of p53 gene alterations in low-grade central osteosarcomas is lower than that in conventional high-grade osteosarcomas. MDM2 alterations and p21WAF1 expression might be involved in the tumorigenesis of low-grade central osteosarcomas.
Department of Pathology, Hallym University, Anyang, Republic of Korea.
Hye-Rim
HR
Park
Woon Won
WW
Jung
Franco
F
Bertoni
Patrizia
P
Bacchini
Jae Hoon
JH
Park
Youn-Wha
YW
Kim
Yong-Koo
YK
Park
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2