Histologically,
desmoplastic small round cell tumor is composed of the characteristic neoplastic small round cells with divergent differentiation, and distinct desmoplastic stroma. Genetically, the
tumor shows a characteristic 11;22 translocation, involving the EWS gene on chromosome 22 and the WT1gene on chromosome 11 to produce an EWS-WT1 fusion gene which generates a chimeric
protein functioning as a novel
transcription factor that activates expression of target genes such as
PDGF-A. Expression of
PDGF-A, a potent
growth factor for fibroblasts, has been detected in desmoplastic small round cell
tumors and has been linked to the characteristic desmoplasia in these
tumors. Bone morphogenic
proteins, which are members of the
TGFbeta superfamily play a complex role in regulating cell growth and differentiation and bone formation but have not been evaluated in desmoplastic small round cell
tumors. In all, 24 desmoplastic small round cell
tumors with EWS-WT1 fusion product confirmed by RT-PCR analysis were evaluated for expression of
PDGF-A, PDGF-Rbeta, TGFbeta3 and bone morphogenic protein-4 by standard immunohistochemical methods with
antigen retrieval on
paraffin sections. Immunoreactivity was evaluated semiquantitively.
Tumor-associated desmoplasia was quantified using a three-tier scale on
hematoxylin- and
eosin-stained sections. Desmoplastic small round cell
tumors showed variable immunoreactivity with TGFbeta3 (21/24), BMP4 (14/21),
PDGF-A (19/24) and PDGF-Rbeta (16/22). Less frequently, the stromal cells showed reactivity with TGFbeta3, PDGF-Rbeta and
PDGF-A.
Tumor-associated desmoplasia was prominent in eight, intermediate in seven and weak in nine cases. There was no correlation between
tumor-associated desmoplasia and the markers tested except
PDGF-A. In contrast to a previous study, our study showed that the level of
PDGF-A expression inversely correlated with
tumor-associated desmoplasia. Other targets of the EWS-WT1
transcription factor other than
PDGF-A may be directly responsible for the prominent
tumor-associated desmoplasia seen in
desmoplastic small round cell tumor.