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KMID : 0613320090150010013
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Journal of the Korean Bone and Joint Tumor Soceity
2009 Volume.15 No. 1 p.13 ~ p.25
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Prognostic Significance of O6-MGMT and Promotor Hypermethylation in Patients with Soft Tissue Sarcomas
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Suh Jeung-Tak
Kim Jeung-Il
Oh Jong-Seok
Choi Kyung-Un
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Abstract
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Purpose: The DNA repair protein, O6-methylguanine-DNA methyltransferase (MGMT), removes alkyl adducts from the O6 position of guanine. Epigenetic inactivation of MGMT has been found in human neoplasia and considered one of the implicated factors in chemoresistance.
Materials and Methods: Sixty-two patiensts with soft tissue sarcomas (STS) were analyzed for the status of MGMT protein expression by immunohistochemistry and the promoter hypermethylation of the MGMT gene using methylation-specific PCR.
Result: The loss of MGMT expression was found in 20 cases (32.3%) of total 62 STS. MGMT promoter hypermethylation rate was 25.0% (11/44 cases). The loss of MGMT expression showed significant association with high AJCC stage, high FNCLCC grade, and aggressive behavior. However,when the group who received chemotherapy was analyzed (n=27), loss of MGMT expression was correlated with worse survival in multivariate analysis (p=0.024). MGMT promoter hypermethylation is associated with high FNCLCC grade. MGMT promoter hypermethylation status had a strong correlation with loss of MGMT expression (p=0.000).
Conclusion: Our results suggest that MGMT promoter hypermethylation and loss of MGMT expression had a tendency to be associated with poor prognosis and that loss of MGMT protein expression is frequently occurs via MGMT promoter hypermethylation.
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KEYWORD
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Soft tissue sarcoma, O6 methylguanine-DNA methyltransferase, Hypermethylation
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