Prognostic roles for fibroblast growth factor receptor family members in malignant peripheral nerve sheath tumor

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.

High amplification of FGFR1 gene is a delayed poor prognostic factor in early stage ESCC patients

“…FGFRs are deregulated by amplification, point mutation, or translocation and amplification is the most common deregulation form in multiple cancer types [ 16 - 18 ]. Amplification of FGFR1 has been reported in 13%-22% squamous cell lung cancer [ 13 , 19 , 20 ], 20% breast cancer [ 12 , 21 ], 10%-17% head and neck squamous cell carcinoma [ 22 , 23 ], and 26.9% malignant peripheral nerve sheath tumor [ 24 ]. FGFR1 amplification induced a strong FGFR1 dependency that could be exploited therapeutically, and in vivo studies have demonstrated inhibition of the FGFR1 pathway with FGFR inhibitors that led to significant tumor shrinkage [ 13 , 25 ], and translational clinical trials are undertaken [ 26 ].…”

Medullary metastasis of a malignant peripheral nerve sheath tumor: A case report

“…Therefore, in the present case, dysphagia and stagger were initially suspected to be side effects of oxycodone treatment. The clinical presentation of brain metastasis is characterized by the acute onset of neurological symptoms (1,7). The clinical symptoms of medullary metastasis may be similar to a medullary infarction, which include dysphagia, dysarthria, dysphonia, vertigo, contralateral deficits in pain and temperature sensation, and vomiting (9).…”

“…Brain metastasis from soft tissue sarcomas, including MPNST, is rare with a reported prevalence of 1-6% of all soft tissue sarcomas (1,4,5). In particular, brain metastasis arising from soft tissue sarcomas, in the absence of lung metastasis, is considered a relatively rare event (1,4,5). Furthermore, to the best of our knowledge, no cases of medullary metastasis without preceding lung metastasis have been reported in the literature to date.…”

“…Despite multimodal treatment, the prognosis of MPNST is poor with 5-year survival rates between 23-69% (3). Brain metastasis from soft tissue sarcomas, including MPNST, is rare with a reported prevalence of 1-6% of all soft tissue sarcomas (1,4,5). In particular, brain metastasis arising from soft tissue sarcomas, in the absence of lung metastasis, is considered a relatively rare event (1,4,5).…”

Platelet-rich plasma and peripheral nerve regeneration: a potential contraindication to its use after tumor excision

“…Let us take for example malignant peripheral nerve sheath tumors (MPNSTs) that arise from major or minor peripheral nerve branches or sheaths of peripheral nerve fibers, and are derived from Schwann cells or pluripotent cells of neural crest origin [2]. Zhou et al [3] investigated the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs via an integrated genomic and molecular study, providing evidence that FGFRs play a role in MPNST prognosis.…”