p53 gene mutations in osteosarcomas of low-grade malignancy

Radig, Kathrin; Schneider‐Stock, Regine; Haeckel, Carsten; Neumann, Wolfram; Roessner, Albert

doi:10.1016/s0046-8177(98)90263-5

Cited by 32 publications

(21 citation statements)

References 22 publications

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“…Our findings support the hypothesis that p53 gene mutations play a part in advanced disease progression, but not in the early tumorigenesis of chondrosarcoma. Thus, the p53 mutation pattern in chondrosarcomas differs from the recently published findings in osteosarcomas, where p53 mutations were found at the same frequency in low-and highmalignancy variants [13].…”

Section: Discussioncontrasting

confidence: 82%

Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma

et al. 2000

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We investigated a dedifferentiated chondrosarcoma of a 61-year-old woman with an osteosarcomatous high-grade component for p53 alteration. The low-grade cartilaginous and the high-grade osteosarcomatous components of the tumor were macrodissected and evaluated separately by immunohistochemistry and molecular biology. We used PCR-SSCP analysis and direct sequencing to screen exons 4-8 for p53 mutations. The p53 intron 1-polymorphism was investigated for loss of heterozygosity. A functionally relevant p53 missense mutation in codon 193 of exon 6 (A-to-T transversion) with loss of wild-type allele was detected only in the dedifferentiated component. Using the monoclonal antibody DO-1, immunohistochemistry failed to show p53 overexpression. This evidence of p53 mutation may be regarded as at least a co-factor that "switched" the preexisting low-grade conventional chondrosarcoma to a highly malignant dedifferentiated tumor.

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Section: Discussioncontrasting

confidence: 82%

Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma

et al. 2000

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“…p53 mutations were found in 15 to 31% of OS cases in previous studies (5,19,(23)(24)(25)(26)(27). Mutations of the p53 gene in patients of Ͻ40 years of age have been reported in 13% (4/30; 24) and 16% (6/38; 13), whereas among those of Ն40 years of age they were seen in 20% (1/5) (24) and 14% (1/7) (14).…”

Section: Discussionmentioning

confidence: 73%

Molecular Analysis of p53, MDM2, and H-ras Genes in Osteosarcoma and Malignant Fibrous Histiocytoma of Bone in Patients Older than 40 Years

et al. 2002

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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 MFHlike 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 formalinfixed 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. Osteosarcoma (OS) is a primary malignant bone tumor that frequently arises in younger patients, occurring less commonly in adults or the elderly (1-3). In contrast, malignant fibrous histiocytoma (MFH) of bone is a malignant bone tumor that frequently arises in adults...

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“…Forty-eight patients (9.6%) had documented metastatic disease at diagnosis. Ten studies stated that osteosarcoma was of high grade (9 -13, 16, 19 -21, 23), one study stated that it was of high or intermediate grade (24), and one study stated that it was of low or intermediate grade (14). No grading information was available in four studies (15,17,18,22).…”

Section: Resultsmentioning

confidence: 99%

“…Nine studies used IHC to determine TP53 status (9, 10, 12, 17-21, 24), four studies used RT-PCR (13,15,22,23), and three studies used both IHC and RT-PCR determinations (11,14,16). One study from those using both RT-PCR and IHC had clinical data only on RT-PCR determinations (14).…”

Section: Resultsmentioning

confidence: 99%

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Prognostic Significance of TP53 Tumor Suppressor Gene Expression and Mutations in Human Osteosarcoma

Pakos

Kyzas

Ioannidis

2004

Clinical Cancer Research

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Purpose: Various studies examining the relationship between tumor suppressor protein TP53 overexpression and/or TP53 gene mutations and the response to chemotherapy and clinical outcome in patients with osteosarcoma have yielded inconclusive results. The purpose of the current study was to evaluate the relation of TP53 status with response to chemotherapy and/or clinical outcome in osteosarcoma.Experimental Design: We conducted a meta-analysis of 16 studies (n ‫؍‬ 499 patients) that evaluated the correlation between TP53 status and histologic response to chemotherapy and 2-year survival. Data were synthesized in summary receiver operating characteristic curves and with summary likelihood ratios (LRs) and risk ratios.Results: The quantitative synthesis showed that TP53 status is not a prognostic factor for the response to chemotherapy. The positive LR was 1.21 (95% confidence interval, 0.86 -1.71), and the negative LR was 0.91 (95% confidence interval, 0.77-1.07). There was no significant between-study heterogeneity. TP53-positive status tended to be associated with a worse 2-year survival, but the overall results were not formally statistically significant. The association was formally significant in studies that clearly stated that measurements were blinded to outcomes (risk ratio, 2.05; 95% confidence interval, 1.23-3.44), and in studies using reverse transcription-PCR for evaluating TP53 alterations (risk ratio, 1.76; 95% confidence interval, 1.07-2.91).Conclusions: TP53 status is not associated with the histologic response to chemotherapy in patients with osteosarcoma, whereas TP53 gene alterations may be associated with decreased survival.

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p53 gene mutations in osteosarcomas of low-grade malignancy

Cited by 32 publications

References 22 publications

Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma

Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma

Molecular Analysis of p53, MDM2, and H-ras Genes in Osteosarcoma and Malignant Fibrous Histiocytoma of Bone in Patients Older than 40 Years

Prognostic Significance of TP53 Tumor Suppressor Gene Expression and Mutations in Human Osteosarcoma

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