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

Background.-Deregulation of tumor suppressor gene function and abrogation o f cell cycle control are common features of malignant neoplasms, but corres ponding data on Ewing sarcomas and primitive neuroectodermal tumors are rel atively 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 o f p16(INK4a), p14(ARF), p21(WAF1), and pRB by immunohistochemical analysis of pretreatment, nondecalcified archival specimens. Clinical follow up was available in all cases (median, 21 months; range, 5-103 months). Five patie nts presented with metastatic disease, 8 had no evidence of disease at last follow up, and 12 had an adverse outcome (death or progressive tumor postt herapy). Results.-Twelve cases (60%) demonstrated abnormal expression of at least on e 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 abse nce 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 meta static disease at presentation or outcome.. Conclusion.-Abrogation of the G1 checkpoint was common in this series of EF Ts, 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.