Immunoexpression of Ezrin and CD44 in patients with osteosarcoma. Metastasis is an important prognostic factor among patients with osteosarcoma. It has been reported that ezrin is important in enabling metastasis and that CD44 expression leads to functional increases in ezrin activation.The aim of this study was to correlate ezrin and CD44 expression with prognosis.Patients with a diagnosis of osteosarcoma who had been treated at Hospital de Cancer de Barretos, Barretos, SP, Brazil, between 2000 and 2005 were selected from the Hospital Tumor Registry. Fifty-two patients and, among these, 34 surgical biopsy specimens of osteosarcoma before chemotherapy were reviewed by the Pathology Department. Ezrin and CD44H protein expression was evaluated using immunohistochemistry on the initial biopsy for these 34 samples.Most patients (76%) were ezrin-positive in cytoplasm and membrane (38.2%); 58.9% presented high-intensity staining and 50.0% had high scores. Half of the patients were CD44H-positive, predominantly in cytoplasm (38.2%); 20.6% presented staining in more than 50% of the cells. None of the markers showed associations with any of the clinicopathologic variables studied. Among the ezrin-positive patients, the 5-year survival rate was 12.8%, whereas it was 41.7% among ezrin-negative patients (P=0.121). The interaction between ezrin and poor histologic response among nonmetastatic patients showed an association with relapse-free 5-year survival of 100% versus 12.7% (P=0.042). The overall survival rates for CD44-positive and negative patients were similar (21.5% and 25.3%, respectively) (P=0.676).Neither CD44H nor ezrin immunoexpression could predict the prognosis for patients with osteosarcoma in our small sample.