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Laboratoire d'Immunobiologie des Tumeurs, CNRS UA 1156, Institut Gustave Roussy, 94805 Villejuif Cedex, France [M. L., K. B., T. T.]; Centre Léon Bérard, 69373 Lyon Cedex, France [I. P., T. P.]; Biochemical Oncology and Membrane Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 [J. W.]; Centre d'Immunologie de Marseille-Luminy, 13288 Marseille Cedex 9, France [C. G.]; and International Agency for Research on Cancer, 69372s Lyon Cedex, France [G. M. L.]
The histogenesis of Ewing's sarcoma, the second most frequent primary bone tumor in humans, remains controversial. Ten Ewing cell lines were analyzed by immunological methods. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. They included ganglioside GD2, a marker of neuroectodermal tissues and tumors, and an acidic glycolipid detected by monoclonal antibody HNK-1 in the nervous system. The P61 rat monoclonal antibody that reacts with a peptide moiety of neural cell adhesion molecule (N-CAM) and a rabbit antiserum raised to purified mouse N-CAM also stained Ewing cells. Flow cytometry analysis performed using these reagents allowed the definition of four distinct Ewing phenotypes: all reagents equally stained group 1 lines; group 2 lines were strongly reactive with anti-N-CAM reagents, by contrast with a fainter staining with HNK-1 and anti-GD2 antibodies; all reagents but P61 were strongly reactive with group 3 lines; in group 4, Ewing lines were stained by P61 but only poorly by the anti-N-CAM antiserum. Several antibodies to melanoma and neuroblastoma associated antigens including two monoclonal antibodies to the nerve growth factor receptor were also found to react with Ewing cells. By contrast, all antibodies detecting antigens specifically expressed in hematopoietic cell lineages were totally unreactive. HLA class II antigens were never detected while the level of expression of class I antigens varied to a large extent. Ewing cells are characterized by a specific t(11;22) (q2324;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor. Thus, Ewing's sarcoma cells share antigenic and karyotypic features with derivatives of the neuroectoderm possibly indicating a related histogenesis.
1 Supported in part by Grants 83D7 from the Institut Gustave Roussy and 2098 from the Association pour la Recherche sur le Cancer.
2 To whom requests for reprints should be addressed.
Received 6/23/86. Accepted 9/22/86.
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