Immunohistochemical detection of EWS and FLI-1 proteinss 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 genes is likely to be of diagnostic value in Ewing sarcoma (ES) and primitive neuroectodermal tumors (PNET). The objective of the current study was to analyze the immunohistochemical expression of the EWS and FLI-1 proteins in a group of small round-cell tumors (SRCT) to determine their specificity and relevance in their differential diagnosis. Forty-eight cases-10 conventional ES, 4 large-cell ES, 5 PNET, 9 neuroblastomas (NB), 6 undifferentiated 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 buffer (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 as 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. EWS 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 types (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 of 5 and 3 of 5 NHL, respectively). Whereas EWS expression does not appear specific 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 diagnosis of SRCT.
Llombart-Bosch
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Department of Pathology, Medical School, University of Valencia, Spain. antonio.llombart@uv.es
Navarro
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D000071443:12E7 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D007150:Immunohistochemistry; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism*; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D034802:RNA-Binding Protein EWS; D012261:Ribonucleoproteins / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015534:Trans-Activators / Q000378:metabolism*
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D034802:RNA-Binding Protein EWS; D012261:Ribonucleoproteins; D015534:Trans-Activators