The histogenesis of Ewing sarcoma, the second most frequent bone tumor in 
humans, remains controversial. Four Ewing cell lines were analyzed by 
immunological methods. A panel of antibodies directed to T, B, and 
myelomonocytic markers gave negative results. Surface antigens recognized on 
Ewing cells were found to be related to the neuroectoderm lineage. Ganglioside 
GD2, a marker of neuroectodermal tissues and tumors, was present on all lines. 
These were also stained by the mouse monoclonal antibody HNK-1, which detects a 
carbohydrate epitope present on several glycoconjugates of the nervous system, 
including two glycoproteins, the myelin-associated glycoprotein and the neural 
cell-adhesion molecule (N-CAM), and an acidic glycolipid of the peripheral 
nervous system. The P61 monoclonal antibody, which reacts with a peptide moiety 
of N-CAM, and a rabbit antiserum, raised to purified mouse N-CAM and not 
recognizing the HNK-1-defined epitope, were also reactive. By contrast, all 
antibodies specific for hematopoietic cell surface antigens were totally 
negative. Besides these antigenic features, Ewing sarcoma cells are 
characterized by a specific t(11;22)(q24;q12) translocation also observed in 
neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary 
related origin. The recent finding that the human N-CAM gene is located at the 
vicinity of the breakpoint on chromosome 11 indicates that it might be involved 
in genetic rearrangements occurring in this region.