EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma
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Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P = 0.004), location (P = 0.046), and EMMPRIN expression (P = 0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P = 0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P = 0.056 for DFS, P = 0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.
KeywordsEMMPRIN Osteosarcoma Matrix metalloproteinase Prognosis
We thank Miss Eri Ishihara for her secretarial assistance. We are also grateful to Drs. Mitsutoshi Uchibori, Eisuke Arai, Satoshi Tsukushi, and Hiroatsu Nakashima for the collection of samples and data. This work was supported in part by the Ministry of Education, Culture, Sports, Science and Technology of Japan [Grant-in-Aid 20591751 for Scientific Research (C)] and by the Suzuken Memorial Foundation.
Conflicts of interest
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