This study aimed to evaluate expression of
receptor tyrosine kinases, their
ligands, and mutational status in
solitary fibrous tumors, with correlation to histopathologic variants,
tumor stage, and aggressive behavior. Immunohistochemical staining for PDGFα; PDGFβ; PDGFR-α; PDGFR-β; IGF1R; EGFR;
VEGF; IGF2; c-Met; c-kit; c-erbB2; PTEN; and phosphorylated (p)AKT, pS6, and p4EBP1 was analyzed in 114 cases of
solitary fibrous tumor using tissue microarray. Mutational analysis was performed using Sequenom MassARRAY-based platform. Multiple
growth factors were overexpressed in most
tumors, and increased numbers of overexpressed factors correlated with activation of the AKT pathway as measured by increased expression of p4EBP1(P = .0005). Compared to hypocellular
tumors, localized hypercellular
tumors were associated with high
vascular endothelial growth factor (32% versus 8%; P = .008) and PDGFβ (41% versus 13%; P = .008). Metastatic
tumors more frequently overexpressed PDGFR-α compared to localized
tumors (75% versus 31%; P < .001). None of the factors examined had prognostic significance in primary
tumors. Single-nucleotide polymorphisms involving MET were identified in 4 patients; these do not appear to drive
tumor behavior and were not reflected in c-Met expression levels. Simultaneous overexpression of multiple
growth factors is common in
solitary fibrous tumors; variability in expression may contribute to
tumor phenotype and aggressive behavior.