K. Froberg et al., Intra-abdominal desmoplastic small round cell tumor: Immunohistochemical evidence for up-regulation of autocrine and paracrine growth factors, ANN CLIN L, 29(1), 1999, pp. 78-85
Citations number
28
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Desmoplastic small round cell turners (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 intesti
nal obstruction. Cytogenetic and molecular studies have identified a charac
teristic t(11;22)(p13;q12) translocation within the tumor cells. The fused
gene product apparently aligns the NH2-terminal domain (NTD) of the EWS gen
e 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 b
y WT1. We investigated this latter possibility by performing immunohistoche
mical studies on formalin fixed tissue from 10 cases of DSRCT and five Wilm
s' tumors using antibodies to insulin-like growth factor (IGF)-II, the late
ncy associated peptide of transforming growth factor (TGF)-beta(1), platele
t-derived growth factor (PDGF)-AB chain and PDGF-alpha receptor, respective
ly. In general, tumor cells were strongly positive for these growth factors
in DSRCT, while stromal cells were negative for IGF-II and positive for th
e other growth factors in parallel with the tumor cells. Wilms' tumor cells
were essentially negative for PDGF-AB chains, hut positive for ICF-II, and
the latency associated peptide of TGF-beta(1) and variably positive for PD
GF-alpha receptor. These findings support the proposed molecular mechanism
of tumorigenesis for DSRCT and may help explain this tumor's poor prognosis
.