Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that ma
y exhibit varied morphologic appearances (spindle, epithelioid) and bi
ologic potentials. Given the continuing controversy regarding the type
of cell differentiation present in these tumors (muscle versus nerve
sheath versus null), we evaluated a set of GISTs, most of which had be
en previously examined for the presence of smooth muscle differentiati
on, for expression of CD34, a 115 kDa cell-surface progenitor cell mar
ker also recently identified in a subset of mesenchymal tumors. Using
antibody My 10 in deparaffinized, formalin-fixed tissue after pretreat
ment with microwave energy, we found that 46 of 57, or 81%, of GISTs w
ere CD34+; this fraction of CD34+ tumors exceeded the fraction of thes
e same GISTs found to show muscle actin (72%) expression. In addition,
a consistently higher fraction of the tumor cell population was CD34 than was muscle actin positive. These findings suggest that CD34 is a
very sensitive marker for the identification of GISTs. CD34 is normal
ly expressed by endothelial as well as perivascular cells, perhaps rel
ated to, but distinct from, vascular smooth muscle cells. While the na
ture of these latter cells is uncertain, the expression of CD34 in suc
h a large fraction of GISTs may provide evidence of a unique different
iation pathway in these tumors.