The clinical significance of changes in ezrin expression in osteosarcoma of children and young adults.

Ezrin is a protein that functions as a cross-linker between actin cytoskeleton and plasma membrane. Its clinical role in osteosarcoma is unclear. The aim of this study was to investigate, in osteosarcoma, the prognostic value of ezrin expression at biopsy and changes in expression levels after preoperative chemotherapy. Thirty-eight newly diagnosed osteosarcoma patients aged 6-23 years were included. At diagnosis, 20 patients had localized disease, the others had distant metastases. Median follow-up was 75 months (range 13-135). Ezrin expression was assessed immunohistochemically in biopsy tissue and primary tumour specimens resected after chemotherapy. The influence on survival of changes in ezrin expression after chemotherapy was analysed. Ezrin expression was significantly higher after preoperative chemotherapy and changes compared to biopsy tissue were significantly lower in patients with early progression than in patients with relapse or no further evidence of disease (p = 0.006 and p = 0.002, respectively). Similarly, ezrin expression was higher after preoperative chemotherapy and exhibited less change in expression in deceased patients compared to patients surviving more than 5 years (both p = 0.001). Ezrin expression at biopsy was significantly associated with both histopathological aggressiveness (p < 0.001) and tumour size (p = 0.037). The results of this study provide evidence that changes in overexpression of ezrin due to preoperative chemotherapy could be a useful predictive and prognostic marker in patients with osteosarcoma.