PMID- 26993773 OWN - NLM STAT- MEDLINE DCOM- 20171204 LR - 20181113 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 16 DP - 2016 Apr 19 TI - Prognostic roles for fibroblast growth factor receptor family members in malignant peripheral nerve sheath tumor. PG - 22234-44 LID - 10.18632/oncotarget.8067 [doi] AB - 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. FAU - Zhou, Wenya AU - Zhou W AD - Department of Bone and Soft Tissue Tumor and Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. AD - National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. FAU - Du, Xiaoling AU - Du X AD - Department of Diagnostics, Tianjin Medical University, Tianjin 300061, People's Republic of China. FAU - Song, Fengju AU - Song F AD - National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. AD - Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. FAU - Zheng, Hong AU - Zheng H AD - National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. AD - Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. FAU - Chen, Kexin AU - Chen K AD - National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. AD - Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. FAU - Zhang, Wei AU - Zhang W AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030 USA. FAU - Yang, Jilong AU - Yang J AD - Department of Bone and Soft Tissue Tumor and Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. AD - National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Biomarkers, Tumor) RN - 0 (Receptors, Fibroblast Growth Factor) RN - EC 2.7.10.1 (FGFR1 protein, human) RN - EC 2.7.10.1 (FGFR2 protein, human) RN - EC 2.7.10.1 (FGFR3 protein, human) RN - EC 2.7.10.1 (FGFR4 protein, human) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 4) SB - IM MH - Adult MH - Aged MH - Biomarkers, Tumor/*analysis MH - Disease-Free Survival MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Neurilemmoma/mortality/*pathology MH - Prognosis MH - Proportional Hazards Models MH - Receptor, Fibroblast Growth Factor, Type 1/analysis/biosynthesis MH - Receptor, Fibroblast Growth Factor, Type 2/analysis/biosynthesis MH - Receptor, Fibroblast Growth Factor, Type 3/analysis/biosynthesis MH - Receptor, Fibroblast Growth Factor, Type 4/analysis/biosynthesis MH - Receptors, Fibroblast Growth Factor/analysis/*biosynthesis MH - Young Adult PMC - PMC5008358 OTO - NOTNLM OT - fibroblast growth factor receptor OT - fluorescence in situ hybridization OT - malignant peripheral nerve sheath tumor OT - microarray-based comparative genomic hybridization OT - prognosis COIS- The authors have no potential conflicts of interest to declare. EDAT- 2016/03/20 06:00 MHDA- 2017/12/05 06:00 PMCR- 2016/04/19 CRDT- 2016/03/20 06:00 PHST- 2016/01/13 00:00 [received] PHST- 2016/02/24 00:00 [accepted] PHST- 2016/03/20 06:00 [entrez] PHST- 2016/03/20 06:00 [pubmed] PHST- 2017/12/05 06:00 [medline] PHST- 2016/04/19 00:00 [pmc-release] AID - 8067 [pii] AID - 10.18632/oncotarget.8067 [doi] PST - ppublish SO - Oncotarget. 2016 Apr 19;7(16):22234-44. doi: 10.18632/oncotarget.8067.