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Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 298 - 299
1 Sep 2005
Fong Y Dutton C Cha S Sim F Dickey I Scully S
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Introduction and Aims: Matrix metalloproteinases can contribute to the processes of tumor invasion and metastasis. One proposed mechanism that could augment MMP-1 expression in individual patients is the existence of an Ets transcription factor-binding site in the MMP-1 promoter sequence. The aim of our study was to identify the prevalence of this single nucleotide polymorphism in chondrosarcoma patients and investigate its impact on disease outcome.

Method: Sixty-seven chondrosarcoma specimens were selected from an established tumor bank. DNA was extracted, amplified with polymerase chain reaction, and sequenced to determine the proportion of genotypes demonstrating the presence (GG) or absence (G) of the SNP at the base pair of interest. The presence of the Ets binding site was correlated with disease-free survival.

Results: Eighteen (27%) samples were G/G homozygous for absence of the Ets site, 34 (51%) were G/GG heterozygous for the SNP, and 15 (22%) were GG/GG homozygous for the SNP. The five-year overall survival rate for patients with the G/G homozygote was 78%, compared with 80% and 84% in patients with the G/GG heterozygotes and GG/GG homozygotes, respectively (p=0.5527). The disease-free survival rate of patients with the G/G genotype were 34%, compared with 74% and 100% in patients with the G/GG and GG/GG genotypes, respectively (p=0.0365).

Conclusion: The disease-free survival in patients having a GG allele was statistically better than the G allele. The observed correlation between the presence of the Ets binding site and better prognosis suggests a down-regulation of MMP-1 expression.