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Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1.

ABSTRACT: Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas with a significant susceptibility to metastasize early in their course. Pathogenesis is yet to be fully elucidated. Recently, the essential role of mast cells in the tumor onset of neurofibromatosis type 1 (NF1)-associated neurofibromas and MPNSTs was confirmed in both experimental and human studies. In this study, we investigate mast cell density (MCD), microvascular density (MVD), and proliferation index (Ki-67) in MPNST. A secondary aim was to correlate histological staining to clinical data and survival in patients with and without NF1. In total, 34 formalin-fixed paraffin-embedded MPNST tissues from 29 patients were eligible. MCD, MVD, and Ki-67 labeling index (LI) were analyzed in all stained tissues by a computer-based quantitative algorithm (Aperio ImageScope). In addition, chart review was performed for clinical data and survival analysis. Overall, MCD, MVD, and Ki-67 LI were evenly distributed throughout tumor tissue. There was a negative correlation of NF1 status (affected, P = 0.037), tumor size (>10 cm, P = 0.023), and MVD in the tumor periphery (higher tercile, P = 0.002) to survival. Multivariate analysis confirmed the association of MVD in the tumor periphery (higher tercile, P = 0.019) with a decreased overall survival. Diverse mast cell and microvascular distributions suggest that angiogenesis in MPNST occurs independently. The role of mast cells in tumor progression is unclear and lacks prognostic value. Higher MVD has prognostic significance with possible therapeutic implications in MPNST.

SUBMITTER: Vasconcelos RAT

PROVIDER: S-EPMC6434338 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1.

Vasconcelos Roberto André Torres de RAT Guimarães Coscarelli Pedro P Vieira Thyago Marsicano TM Noguera Washington Silva WS Rapozo Davy Carlos Mendes DCM Acioly Marcus André MA

Cancer medicine 20190208 3

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas with a significant susceptibility to metastasize early in their course. Pathogenesis is yet to be fully elucidated. Recently, the essential role of mast cells in the tumor onset of neurofibromatosis type 1 (NF1)-associated neurofibromas and MPNSTs was confirmed in both experimental and human studies. In this study, we investigate mast cell density (MCD), microvascular density (MVD), and proliferation i ...[more]

PMID: 30735009

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Project description:IntroductionMalignant peripheral nerve sheath tumors (MPNSTs) are malignancies that demonstrate nerve sheath differentiation in the peripheral nervous system. They can occur sporadically or be associated with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder, with up to 13% of patients developing MPNSTs in their lifetimes. Previous studies have suggested conflicting findings regarding the prognosis of NF1 for patients with MPNSTs. The elucidation of NF1 as an independent prognostic factor on mortality has implications for clinical management. We aim to investigate the role of NF1 status as an independent prognostic factor of overall survival (OS) and disease-specific survival (DSS) in MPNSTs.MethodsAn electronic literature search of PubMed and MEDLINE was performed on studies reporting OS or DSS outcomes of MPNSTs with and without NF1. A grey literature search by reviewing bibliographies of included studies and review articles was performed to find pertinent studies. Data was extracted and assessed in accordance with the PRISMA guidelines. A meta-analysis was performed to calculate hazard ratios (HRs) using a random-effects model. The primary and secondary outcomes were all-cause and disease-specific mortality, respectively, with NF1 as an independent prognostic factor of interest.ResultsA total of 59 retrospective studies involving 3602 patients fulfilled the inclusion criteria for OS analysis, and 23 studies involving 704 MPNST patients were included to evaluate DSS outcomes. There was a significant increase in the hazard of all-cause mortality (HR 1.63, 95% CI 1.45 to 1.84) and disease-specific mortality (HR 1.52, 95% CI 1.24 to 1.88) among NF1 as compared to sporadic cases. Subgroup analyses and meta-regression showed that this result was consistent regardless of the quality of the study and year of publication.ConclusionNF1 is associated with a substantially higher risk of all-cause and disease-specific mortality. This finding suggests that closer surveillance is required for NF1 patients at risk of developing MPNSTs.

Project description:BACKGROUND: Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome characterized by the development of benign nerve-sheath tumors, which transform to malignant peripheral nerve-sheath tumors (MPNST) in about 8 to 13% of patients with NF1. MPNST are invasive sarcomas with extremely poor prognosis, and their development may correlate with internal tumor load of patients with NF1. Because early identification of patients with NF1 at risk for developing MPNST should improve their clinical outcome, the aim of this study was to identify serum biomarkers for tumor progression in NF1, and to analyze their correlation with tumor type and internal tumor load. METHODS: We selected candidate biomarkers for NF1 by manually mining published data sources, and conducted a systematic screen of 56 candidate serum biomarkers using customized antibody arrays. Serum from 104 patients with NF1 with and without MPNST, and from 41 healthy control subjects, was analyzed. Statistical analysis was performed using the non-parametric Mann-Whitney U-test, followed by Bonferroni correction. RESULTS: Our analysis identified four markers (epidermal growth factor receptor, interferon-?, interleukin-6, and tumor necrosis factor-?) for which significantly different serum concentrations were seen in patients with NF1 compared with healthy controls. Two markers (insulin-like growth factor binding protein 1 (IGFBP1) and regulated upon activation, normal T-cell expressed and secreted (RANTES)) showed significantly higher concentrations in patients with NF1 and MPNST compared with patients with NF1 without MPNST. A correlation with internal tumor load was found for IGFBP1. CONCLUSION: Our study identified two serum markers with potential for early detection of patients with NF1 at risk for developing MPNST, and four markers that could distinguish between patients with NF1 and healthy subjects. Such markers may be useful as diagnostic tools to support the diagnosis of NF1 and for timely identification of MPNST. Moreover, the data suggest that there is a systemic increase in inflammatory cytokines independently of tumor load in patients with NF1.

Dataset Information

Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1.

Publications

Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1.

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