Immunohistochemical detection of EWS and FLI-1 proteins in ewing sarcoma and primitive neuroectodermal tumors: Comparative analysis with CD99 (MIC-2)expression

The molecular analysis of the t(11;22) rearrangement involving EWS/FLI-1 ge nes is likely to be of diagnostic value in Ewing sarcoma (ES) and primitive neuroectodermal tumors (PNET). The objective of the current study was to a nalyze the immunohistochemical expression of the EWS and FLI-1 proteins in a group of small round-cell tumors (SRCT) to determine their specificity an d relevance in their differential diagnosis. Forty-eight cases - 10 convent ional ES, 4 large-cell ES, 5 PNET, 9 neuroblastomas (NB), 6 undifferentiate d synovial sarcomas (SS), 5 rhabdomyosarcomas (RB), 5 non-Hodgkin lymphomas (NHL), 1 round-cell liposarcoma. and 3 mesenchymal chondrosarcomas - were analyzed. Immunocytochemistry was performed on paraffin sections after the LSAB method and antigen retrieval using ethylenediaminetetraacetic acid buf fer (pH 6). Primary antibodies included FLI-1 (C-19), EWS (N-18), EWS (C-19 ), and CD99 (MIC-2). As expected, CD-99 expression was found in 100% of ES/ PNET cases, in 2 cases of RB, 2 SS, and 1 NHL. FLI-1 protein was observed a s nuclear staining in 16 cases of ES/PNET (84%) and in 4 cases of NHL, 2 NB , and 3 SS. Normal endothelial cells and lymphocytes also were positive. EW S expression (both proteins N-18 and C-19) was detected not only in 95% of ES/PNET cases but also in more than 50% of cases from the other tumoral typ es (4 of 9 and 7 of 9 NB,5 of 6 and 6 of 6 SS, 3 of 5 and 5 of 5 RB,and 2 o f 5 and 3 of 5 NHL, respectively). Whereas EWS expression does not appear s pecific for ES/PNET, analysis of FLI-1 expression together with CD-99 is a powerful marker for ES/PNET and important factors in the differential diagn osis of SRCT.