Relation of neuroglial marker expression and EWS gene fusion types in MIC2/CD99-positive tumors of the Ewing family

The Ewing family of tumors (EFT) is characterized by high MIC2/CD99 express ion and specific EWS/ETS gene rearrangements, resulting in different chimer ic transcripts. Further division into peripheral primitive neuroectodermal tumors and Ewing's sarcoma is still debated and, in the absence of distinct morphological parameters, has been based on the reactivity with neuroglial markers (NgM). We investigated 44 EFT in terms of a possible correlation b etween the type of EWS chimeric transcripts and reactivity with the followi ng NgM: polyclonal and monoclonal neuron-specific enolase (NSE), S-100, chr omogranin A, synaptophysin, Leu-7, glial fibrillary acid protein, and neuro filament. EWS/Fli1 fusion type 1 was detected in 30 of 44 and type 2 in 11 of 44 tumors. Three tumors, presenting with an uncommon morphology, carried rare chimeric transcripts. Our results indicate an association of lack of Ng bl staining with type 1 EWS/Fli1 translocations, found in 16 of 18 rumor s with no NgM expression as detectable by any of the antibodies we applied. Using the monoclonal NSE antibody, 21 of 26 tumors without NgM staining ex pressed type 1 EWS/FLI1 chimeric RNA, whereas in the groups with 1 or more and 2 or more NgM, only 9 of 17 and 1 of 5 tumors, respectively carried typ e 1 EWS/FLi1 fusion transcripts. Despite this association of increased NgM expression with a non-type I EWS/Fli1 gene fusion, a strict correlation bet ween the extent of NgM expression and certain EWS fusion types was not evid ent. This fortifies the concept to consider EFT as a spectrum of tumors and suggests the type of EWS fusion transcripts as one, but not the only param eter influencing the extent of differentiation. HUM PATHOL 30:1058-1064. Co pyright (C) 1999 by W.B. Saunders Company.