title: Prognostic roles for fibroblast growth factor receptor family members in malignant peripheral nerve sheath tumor.
abstract: BACKGROUND
  Malignant peripheral nerve sheath tumors (MPNST) are rare, highly malignant, and poorly understood sarcomas. The often poor outcome of MPNST highlights the necessity of identifying prognostic predictors for this aggressive sarcoma. Here, we investigate the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs.
  
  
  RESULTS
  aCGH and bioinformatics analysis identified frequent amplification of the FGFR1 gene. FISH analysis revealed that 26.9% MPNST samples had amplification of FGFR1, with both focal and polysomy patterns observed. IHC identified that FGFR1 protein expression was positively correlated with FGFR1 gene amplification. High expression of FGFR1 protein was associated with better overall survival (OS) and was an independent prognostic predictor for OS of MPNST patients. Additionally, combined expression of FGFR1 and FGFR2 protein characterized a subtype of MPNST with better OS. FGFR4 protein was expressed 82.3% of MPNST samples, and was associated with poor disease-free survival.
  
  
  METHODS
  We performed microarray-based comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Medical University Cancer Institute and Hospital. Fluorescence in situ hybridization (FISH) was used to validate the gene amplification detected by aCGH analysis. Another cohort of 63 formalin-fixed paraffin-embedded MPNST samples (including 52 samples for FISH assay) was obtained to explore FGFR1, 2, 3, and 4 protein expression by immunohistochemical (IHC) analysis.
  
  
  CONCLUSIONS
  Our integrated genomic and molecular studies provide evidence that FGFRs play different prognostic roles in MPNST.
authors.affiliation: Department of Bone and Soft Tissue Tumor and Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.|National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.
authors.forename: Wenya
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Diagnostics, Tianjin Medical University, Tianjin 300061, People's Republic of China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Du
authors.affiliation: National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.|Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.
authors.forename: Fengju
authors.initials: F
authors.lastname: Song
authors.affiliation: National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.|Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.|Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030 USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Bone and Soft Tissue Tumor and Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.|National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.
authors.forename: Jilong
authors.initials: J
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000032:analysis / Q000096:biosynthesis; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000032:analysis / Q000096:biosynthesis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000032:analysis / Q000096:biosynthesis; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000032:analysis / Q000096:biosynthesis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; C496371:FGFR4 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051499:Receptor, Fibroblast Growth Factor, Type 4
keywords: fibroblast growth factor receptor; fluorescence in situ hybridization; malignant peripheral nerve sheath tumor; microarray-based comparative genomic hybridization; prognosis