Ewing sarcoma family tumors (ESFT) are highly undifferentiated bone and soft tissue tumors that primarily affect children. Metastatic disease at diagnosis portends a worse prognosis and remains the only reliable predictor of outcome. The polycomb protein BMI-1 is associated with worse clinical outcome in some human cancers. This study evaluates the clinical and biologic significance of BMI-1 expression in ESFT.

Using immunohistochemical analysis, 80% of ESFT were found to robustly express BMI-1 in all tumor cells, while 15% lacked BMI-1 expression. Analysis of 79 tumors revealed no association between BMI-1 and clinical presentation, outcome, loss of p16 or mutation of p53. Significantly, however, BMI-1 levels were highly inversely correlated with markers of neural crest differentiation. Together these findings demonstrate that ESFT cells nearly universally express BMI-1 and suggest that high-level expression of BMI-1 underlies the highly undifferentiated phenotype that characterizes this tumor family.