Expression of matrix metalloproteinase regulator, RECK, and its clinical significance in osteosarcoma. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a novel membrane-anchored matrix metalloproteinase inhibitor, have been shown to be associated with prognosis and suppress tumor progression through angiogenesis inhibition in many cancers. In this study, the expression of RECK in osteosarcoma was examined, and its clinical significance was firstly evaluated. RECK expression was immunohistochemically examined in osteosarcoma from 49 patients. By summing intensity and proportion scores, these patients were categorized as weak and strong. RECK expression in the primary tumor was strong in 27 patients (55.1%) and was weak in the rest of the patients. The 5-year survival rate of patients with RECK-strong tumor (81.5%) was significantly higher than that of patients with RECK-weak tumor (36.4%; p = 0.003). Reduced RECK expression significantly correlated with metastasis (p = 0.010) and recurrence (p = 0.004). A multivariate analysis confirmed that reduced RECK expression was an independent and significant factor to predict a poor prognosis (p = 0.017). RECK status is a useful prognostic factor in osteosarcoma, and an independent prognostic factor contributing to the determination of more adequate therapy strategies for each patient.© 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.