Abstract
BackgroundMalignant 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.ResultsaCGH 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 MethodsWe 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.ConclusionsOur integrated genomic and molecular studies provide evidence that FGFRs play different prognostic roles in MPNST.
Highlights
Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant sarcomas derived from the neural crest and account for approximately 5–10% of all soft tissue sarcomas [1, 2]
We evaluated the prognostic value of fibroblast growth factor receptor (FGFR) expression in MPNST using a microarray‐based comparative genomic hybridization method, fluorescence in situ hybridization (FISH), and immunohistochemical (IHC) methods to evaluate the gene status and protein expression levels of FGFR1–4 in MPNST samples
Combined high expression of FGFR1 and FGFR2 protein characterized a subtype of MPNST with better overall survival (OS), while increased FGFR4 protein expression predicted worse disease‐free survival (DFS)
Summary
Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant sarcomas derived from the neural crest and account for approximately 5–10% of all soft tissue sarcomas [1, 2]. MPNSTs occur either sporadically or in association with neurofibromatosis type 1 (NF1). The overall incidence of MPNST in the general population is 1/100000, of which 5–42% are associated with NF1 [2]. The prognosis for patients with MPNST remains very poor [3]. Identification of novel prognostic features and therapeutic strategies are required to benefit patients with this aggressive sarcoma. 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. We investigate the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs
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