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Human pathology

Histologic variability in solitary fibrous tumors reflects angiogenic and growth factor signaling pathway alterations.


PMID 25976141

Abstract

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.