Aberrant expression of tumor suppressor proteins in the Ewing family of tumors

Background. - Deregulation of tumor suppressor gene function and abrogation of cell cycle control are common features of malignant neoplasms, but corresponding data on Ewing sarcomas and primitive neuroectodermal tumors are relatively scarce. We studied the expression of 4 tumor suppressor proteins in the Ewing family of tumors (EFTs). Design. - We examined a series of 20 pediatric EFTs for abnormal expression of p16^INK4a, p14^ARF, p21^WAF1, and pRB by immunohistochemical analysis of pretreatment, non-decalcified archival specimens. Clinical follow up was available in all cases (median, 21 months; range, 5-103 months). Five patients presented with metastatic disease, 8 had no evidence of disease at last follow up, and 12 had an adverse outcome (death or progressive tumor posttherapy). Results. - Twelve cases (60%) demonstrated abnormal expression of at least one tumor suppressor protein. There were 11 cases (55%) with loss of p21^WAF1 expression, 4 (20%) with down-regulation of p16^INK4a, 2 (10%) with absence of pRB, and one case (5%) with loss of p14^ARF expression. Loss of p16^INK4a expression correlated with metastatic disease at presentation (P = .026), and showed a trend toward shortened survival (P = .20). The p21^WAF1, p14^ARF, and pRB status was not significantly correlated with either metastatic disease at presentation or outcome. Conclusion. - Abrogation of the G1 checkpoint was common in this series of EFTs, and down-regulation of p21^WAF1 and p16^INK4a were the most frequent findings. Loss of p16^INK4a expression may identify a subset of cases with a more aggressive phenotype.