Cancer Res Treat.  2005 Dec;37(6):360-364.

Overexpression of Metastatic Tumor Antigen in Osteosarcoma: Comparison between Conventional High-Grade and Central Low-Grade Osteosarcoma

• Park HR
• Jung WW
• Kim HS
• Bacchini P
• Bertoni F
• Park YK

Abstract

PURPOSE
The metastatic tumor antigen (MTA) gene is a recently identified metastasis-associated gene which has implications in the signal transduction or regulation of gene expression. However, the expression of MTA in osteosarcoma and its potential relationship with metastasis have not been examined, forming the basis of this study. MATERIALS AND METHODS: We compared the expression levels of the MTA1 protein between 32 cases of high- grade osteosarcomas and 21 cases of low-grade osteosarcomas by immunohistochemistry. In addition, the mRNA expression levels of MTA1, 2, 3 in these osteosarcoma cell lines and control fibroblasts were evaluated by real-time quantitative PCR. RESULTS: MTA1 immunoreactivity was present in 81.25% of high-grade osteosarcoma specimens. Its expression was predominantly localized to the nucleus or cytoplasm of osteosarcoma cells. Thirteen (86.6%) of 15 patients who died of osteosarcomas displayed strong MTA1 expression. Both primary bone and pulmonary metastatic lesions exhibited MTA1 expression. All low- grade osteosarcomas were negative for MTA1 except for focal weak reactivity in two cases. The tested high-grade osteosarcoma cell lines showed marked amplification of MTA1 and MTA2 mRNA compared to control cells. CONCLUSION: These results suggest that MTA might be involved in the progression of high-grade osteosarcoma, particularly in hematogenous metastasis of osteosarcoma.

Keyword

Metastatic tumor antigen (MTA); Osteosarcoma

MeSH Terms

Cell Line
Cytoplasm
Fibroblasts
Gene Expression Regulation
Humans
Immunohistochemistry
Neoplasm Metastasis
Osteosarcoma*
Polymerase Chain Reaction
RNA, Messenger
Signal Transduction
Pemetrexed
RNA, Messenger

Figure

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  Fig. 1 Immunohistochemistry for MTA1 in primary bone lesion of conventional high-grade osteosarcoma. Diffuse, strong expression was noted in the nucleus and cytoplasm of irregular pleomorphic tumor cells (original magnification, ×200).

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  Fig. 2 Immunohistochemistry for MTA1 in pulmonary metastatic tumor sample of high-grade osteosarcoma (original magnification, ×200).

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  Fig. 3 Immunohistochemistry for MTA1 in low-grade central osteosarcoma. All the tumor cells were negative (original magnification, ×200).

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  Fig. 4 Amplification curves for the MTA1 mRNA in osteosarcoma cell lines and control fibroblast by real-time quantitative PCR. All three osteosarcoma cell lines showed an average 8-fold higher amplification of MTA1 mRNA compared to the control.

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