Prognostic roles for fibroblast growth factor receptor family members in malignant peripheral nerve sheath tumor
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Wenya Zhou1,2,*, Xiaoling Du3,*, Fengju Song2,4, Hong Zheng2,4, Kexin Chen2,4, Wei Zhang5, Jilong Yang1,2
1Department of Bone and Soft Tissue Tumor and Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People’s Republic of China
2National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People’s Republic of China
3Department of Diagnostics, Tianjin Medical University, Tianjin 300061, People’s Republic of China
4Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People’s Republic of China
5Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030 USA
*These authors contributed equally to this work
Jilong Yang, e-mail: [email protected]
Keywords: malignant peripheral nerve sheath tumor, fibroblast growth factor receptor, prognosis, microarray-based comparative genomic hybridization, fluorescence in situ hybridization
Received: January 13, 2016 Accepted: February 24, 2016 Published: March 14, 2016
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.
Materials and 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.
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