EXPRESSION OF DEVELOPMENTALLY-REGULATED MUSCLE PROTEINS IN RHABDOMYOSARCOMAS

Human skeletal muscle differentiation and maturation follows a precise sequence of events. To investigate whether and to what extent rhabdom yosarcoma (RMS) cells follow a comparable sequence, 29 fresh frozen sp ecimens of RMS (14 primaly and 15 relapses) were immunostained with an tibodies directed against developmentally regulated myosin heavy chain s (MHC), ie, fetal, fast, and slow MHC, in addition to desmin and vime ntin. Four distinct patterns of expression were observed: I) RMS cells expressing exclusively vimentin and desmin (n = 7), II) in addition t o expression of vimentin and desmin, a minority of neoplastic cells we re immunoreactive with fetal MHC (n = 6), III) in addition to pattern II, fast MHC was expressed (n = 7), and IV) RMS cells simultaneously e xpressing vimentin, desmin, fetal, fast, and slow MHC (n = 9). Accordi ngly, the proportion of the MHC immunoreactive RMS cells increased gra dually along with the four patterns of expression evolving from less t han 25% up to 75% for fetal MHC, from less than 25% up to 50% for fast MHC, and up to 25% for slow MHC in the last category. Vimentin and de smin were coexpressed by almost all RMS cells. Double immunostaining r evealed that comparable with the myogenic cells in the developing feta l skeletal muscle, expression of fetal MHC could be demonstrated in th e same neoplastic cells either in conjunction with fast or slow MHC. I n contrast, only in RMS, slow MHC expression in conjunction with fast MHC could be observed in the neoplastic cells. Neither the shape or si ze of neoplastic RMS cells, nor the histopathological types, nor tumor localization were related to the expression pattern of developmentall y regulated MHC (fetal, fast, and slow MHC). These results confirm the commitment of the RMS cells to the myogenic pathway and demonstrate a restricted and aberrant differentiation pattern of the neoplastic cel ls in RMS compared with normal myogenesis, independent of histopatholo gical types of RMS.