OLFACTORY NEUROBLASTOMA IS NOT RELATED TO THE EWING FAMILY OF TUMORS - ABSENCE OF EWS FLI1 GENE FUSION AND MIC2 EXPRESSION/

The relationship of olfactory neuroblastoma to the Ewing sarcoma famil y of tumors remains controversial due to its variable histopathology a nd to conflicting or inconsistent cytogenetic, immunophenotypic, and m olecular data. To address this issue, we performed a morphologic, immu nohistochemical, and molecular study of 20 olfactory neuroblastomas. M orphologically, the tumors consisted of nests of primitive small, roun d, blue cells, usually set in a background of neurofibrillary stroma. Immunohistochemical stains revealed strong reactivity for neuroendocri ne markers (synaptophysin, chromogranin, neuronspecific enolase) and o nly focal staining for cytokeratins in two cases. Immunostaining with antibody O13 to the Ewing sarcoma-associated MIC2 antigen was uniforml y negative (0 of 17). Amplifiable RNA was extracted from paraffin-embe dded tissue blocks of 11 cases, and no evidence of the chimeric EWS/FL I transcript, characteristic of Ewing sarcoma, was found in any case. The EWS gene was not rearranged using Southern blot analysis in one ad ditional case in which high molecular weight DNA was available. These results disagree with the proposed classification of olfactory neurobl astoma in the Ewing sarcoma family of tumors and suggest that therapy developed for the latter tumor group may not be biologically rational for olfactory neuroblastoma.