Intra-abdominal desmoplastic small round cell tumor: immunohistochemical evidence for up-regulation of autocrine and paracrine growth factors

Desmoplastic small round cell tumors (DSRCT) are highly aggressive tumors typically involving the serosal surfaces of the peritoneum. Patients often present with abdominal pain, an abdominal mass, ascites or signs of intestinal obstruction. Cytogenetic and molecular studies have identified a characteristic t(11;22)(p13;q12) translocation within the tumor cells. The fused gene product apparently aligns the NH2-terminal domain (NTD) of the EWS gene to the zinc finger DNA-binding domain of the WT1 gene. This product could lead to loss of the tumor suppressor effect of the WT1 gene as well as to an increase in EWS driven expression of growth factors normally repressed by WT1. We investigated this latter possibility by performing immunohistochemical studies on formalin fixed tissue from 10 cases of DSRCT and five Wilms' tumors using antibodies to insulin-like growth factor (IGF)-II, the latency associated peptide of transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-AB chain and PDGF-alpha receptor, respectively. In general, tumor cells were strongly positive for these growth factors in DSRCT, while stromal cells were negative for IGF-II and positive for the other growth factors in parallel with the tumor cells. Wilms' tumor cells were essentially negative for PDGF-AB chains, but positive for IGF-II, and the latency associated peptide of TGF-beta1 and variably positive for PDGF-alpha receptor. These findings support the proposed molecular mechanism of tumorigenesis for DSRCT and may help explain this tumor's poor prognosis.