title: Histologic variability in solitary fibrous tumors reflects angiogenic and growth factor signaling pathway alterations.
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.
authors.affiliation: Department of Pathology, Mount Sinai Hospital, New York, NY 10029. Electronic address: Elizabeth.Demicco@mountsinai.org.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Demicco
authors.affiliation: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030.
authors.forename: Khalida
authors.initials: K
authors.lastname: Wani
authors.affiliation: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Fox
authors.affiliation: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030.
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.affiliation: Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Young
authors.affiliation: Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030.
authors.forename: Dina
authors.initials: D
authors.lastname: Lev
authors.affiliation: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.affiliation: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030; Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.affiliation: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston TX 70030.
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042501:Angiogenic Proteins / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D049109:Cell Proliferation; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009389:Neovascularization, Pathologic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D054364:Solitary Fibrous Tumors / Q000098:blood supply* / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D046888:Tissue Array Analysis; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D042501:Angiogenic Proteins; D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins
keywords: Angiogenesis; Growth factor; Hemangiopericytoma; Oncogenesis; Solitary fibrous tumor; Targeted therapy