Rhabdomyosarcomas are a heterogeneous group of
tumors with respect to their molecular basis, degree of differentiation, histology, and clinical behavior. Because of the wide variation of
tumor morphology, it is often difficult to distinguish between the distinct subtypes of
rhabdomyosarcomas. By using cryosections of
tumor specimens and immunohistochemistry, in the present study we show that strong expression of
myogenin in
rhabdomyosarcoma is associated with alveolar histology (P = <0.0001, Fisher's exact test). Although staining for
myogenin was observed in 22 of 26
rhabdomyosarcomas, all
alveolar rhabdomyosarcomas (nine of nine) showed high levels of staining for
myogenin, as defined by the frequency and intensity of staining of the
tumor cells. The staining pattern suggests that the
tumor cells are clonally derived from
myogenin-positive progenitor cells. In contrast, most
embryonal rhabdomyosarcomas (13 of 15) were either negative or showed a low level of staining for
myogenin. In these
tumors a larger proportion of
tumor cells were distinctly negative for
myogenin. Six of seven
alveolar rhabdomyosarcomas that strongly stained for
myogenin were also positive for Pax3-7/Forkhead (FKHR) by polymerase chain reaction/
reverse transcriptase-polymerase chain reaction. One of two
embryonal rhabdomyosarcomas that strongly stained for
myogenin was retrospectively found to be positive for Pax3/FKHR transcripts. Quantitative analysis for
myogenin by Western blotting using a smaller subset of
rhabdomyosarcomas revealed that in general there was a good correlation between immunohistochemical staining and Western blotting (P = 0.01, Pearson Correlation), although the former technique was more sensitive for detecting
tumors with low levels of the
protein. On average,
alveolar rhabdomyosarcomas expressed at least threefold more
myogenin than
embryonal rhabdomyosarcomas. Our data show that staining for
myogenin will be a simple, rapid, and accurate adjunct for distinguishing between alveolar and
embryonal rhabdomyosarcomas. We propose that
embryonal rhabdomyosarcomas result from an early block in myogenesis, before the expression of
myogenin. In contrast, we propose that
alveolar rhabdomyosarcomas either originate from a late block in myogenesis (after expression of
myogenin) or that the pathological mechanisms involved in these
neoplasms also induce strong expression of this
protein.