There is increasing evidence that
WT1 protein expression is found not only at nuclear, but also at cytoplasmic, level in several developing and neoplastic tissues. In order to better understand the possible role of
WT1 protein in human skeletal myogenesis and
oncogenesis of
rhabdomyosarcoma, we assessed immunohistochemically its comparative expression in a large series of human developing, adult and neoplastic skeletal muscle tissues. The present study shows that
WT1 protein is developmentally expressed in the cytoplasm of human myoblasts from the 6 weeks of gestational age. This expression was maintained in the myotubes of developing muscles of the trunk, head, neck, and extremities, while it was down-regulated in fetal skeletal fibers from 20 weeks of gestational age as well as in adult normal skeletal muscle. Notably, WT1 immunostaining disappeared from
rhabdomyomas, whereas it was strongly and diffusely re-expressed in all cases (27/27) of embryonal and
alveolar rhabdomyosarcoma. The comparative evaluation of the immunohistochemical findings revealed that WT1 cytoplasmic expression in
rhabdomyosarcoma may represent an ontogenetic reversal, and this nuclear
transcription factor can also be considered an oncofetal
protein which can be exploitable as an additional, highly sensitive immunomarker, together with
desmin,
myogenin and MyoD1, of this
tumor. Moreover, our observations support the rationale for the use of
WT1 protein-based target
therapy in high risk
rhabdomyosarcomas in children and adolescents.