| Molecular analysis of p53, MDM2, and H-ras genes in osteosarcoma and malignant fibrous histiocytoma of bone in patients older than 40 years. | |
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MedLine Citation:
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PMID: 12181274 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Some investigators have reported that the histological features of osteosarcoma (OS) arising in elderly patients are different from those in younger patients; however, a molecular biologic study of OS in elderly patients has not been documented. In this study, 23 cases of OS (15 osteoblastic and 8 MFH-like types) and 18 cases of MFH of bone in patients 40 years of age or older were analyzed for mutation of the p53 gene, amplification of the MDM2 gene, and mutation 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 proliferative activities using the monoclonal antibody MIB-1. p53 immunoreactivity was recognized in 5 of 23 OS cases (22%), whereas p53 gene mutations were also detected in 5 of 23 OS cases (22%; osteoblastic [4/15; 27%] and MFH-like [1/8; 18%] types) and in 4 of 18 cases of MFH of bone (22%). There was a statistically significant correlation between p53 immunoreactivity and p53 mutation status in OS (P =.0482). All those cases of osteoblastic OS and MFH of bone that had p53 mutations, with the exception of one case of MFH of bone that had a silent mutation, showed aggressive biologic behavior (dead of disease within 12 mo), in contrast to the MFH-like OS cases (alive without disease at 22 mo). Three cases of OS (13%) and three cases of MFH of bone (17%) showed immunoreactivity for MDM2. As for gene alteration, three cases of OS (13%) and 3 cases of MFH of bone (17%) demonstrated MDM2 amplification. MDM2 amplification showed a significant correlation with the expression of MDM2 protein in OS (P =.0344). p21WAF1 expression was detected in three cases of OS (13%) and in six cases of MFH of bone (33%). MDM2 alteration and p21WAF1 expression were not observed in any of the cases of MFH-like OS. MIB-1-LI showed a statistically significant correlation with p53 immunoreactivity and MDM2 immunoreactivity in OS (P =.0307 and P =.0358, respectively). H-ras mutation at Codons 12 and 13 was not recognized in any of the cases of OS or MFH of bone. In conclusion, although treatment differences during the time of study make it difficult to compare survival analysis, in the current study, p53 mutation in osteoblastic OS and MFH of bone in elderly patients seemed to be closely associated with the progression of the tumor, which was not the case in MFH-like OS. Furthermore, MDM2 alteration and p21WAF1 expression were demonstrated only in osteoblastic OS and MFH of bone, whereas they were not recognized in MFH-like OS. Although the number of patients in this analysis was small, it would appear that MFH-like OS may have some characteristic biologic aspects when compared with osteoblastic OS and MFH of bone in elderly patients. |
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Authors:
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Ken-ichi Kawaguchi; Yoshinao Oda; Akio Sakamoto; Tsuyoshi Saito; Sadafumi Tamiya; Yukihide Iwamoto; Masazumi Tsuneyoshi |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Volume: 15 ISSN: 0893-3952 ISO Abbreviation: Mod. Pathol. Publication Date: 2002 Aug |
Date Detail:
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Created Date: 2002-08-15 Completed Date: 2003-02-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8806605 Medline TA: Mod Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 878-88 Citation Subset: IM |
Affiliation:
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Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Age Factors Aged Bone Neoplasms / genetics*, metabolism, pathology Cyclin-Dependent Kinase Inhibitor p21 Cyclins / biosynthesis DNA Mutational Analysis DNA, Neoplasm / analysis* Female Gene Amplification Genes, p53 / genetics, physiology Genes, ras / genetics Histiocytoma, Benign Fibrous / genetics*, metabolism, pathology Humans Immunohistochemistry Ki-67 Antigen / biosynthesis Male Middle Aged Mutation* Nuclear Proteins* Osteosarcoma / genetics*, metabolism, pathology Polymerase Chain Reaction Prognosis Proto-Oncogene Proteins / biosynthesis, genetics Proto-Oncogene Proteins c-mdm2 |
| Chemical | |
Reg. No./Substance:
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0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/DNA, Neoplasm; 0/Ki-67 Antigen; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2 |
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