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 neurofibromatos...

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Main Authors: Roberto André Torres de Vasconcelos, Pedro Guimarães Coscarelli, Thyago Marsicano Vieira, Washington Silva Noguera, Davy Carlos Mendes Rapozo, Marcus André Acioly
Format: Article
Language:English
Published: Wiley 2019-03-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.1977
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author Roberto André Torres de Vasconcelos
Pedro Guimarães Coscarelli
Thyago Marsicano Vieira
Washington Silva Noguera
Davy Carlos Mendes Rapozo
Marcus André Acioly
author_facet Roberto André Torres de Vasconcelos
Pedro Guimarães Coscarelli
Thyago Marsicano Vieira
Washington Silva Noguera
Davy Carlos Mendes Rapozo
Marcus André Acioly
author_sort Roberto André Torres de Vasconcelos
collection DOAJ
description 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.
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spelling doaj-art-1e7d3b33a6404a3ba09eb12727f6538a2025-01-31T08:47:42ZengWileyCancer Medicine2045-76342019-03-018397298110.1002/cam4.1977Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1Roberto André Torres de Vasconcelos0Pedro Guimarães Coscarelli1Thyago Marsicano Vieira2Washington Silva Noguera3Davy Carlos Mendes Rapozo4Marcus André Acioly5Division of Bone and Connective Tissue, Department of Surgical Oncology National Cancer Institute Rio de Janeiro BrazilDivision of Internal Medicine State University of Rio de Janeiro Rio de Janeiro BrazilDivision of Pathology National Cancer Institute Rio de Janeiro BrazilDivision of Pathology National Cancer Institute Rio de Janeiro BrazilDivision of Pathology National Cancer Institute Rio de Janeiro BrazilPostgraduation Program in Neurology Federal University of the State of Rio de Janeiro Rio de Janeiro BrazilAbstract 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.https://doi.org/10.1002/cam4.1977malignant peripheral nerve sheath tumormast cellmast cell densitymicrovascular densityneoangiogenesisneurofibromatosis type 1
spellingShingle Roberto André Torres de Vasconcelos
Pedro Guimarães Coscarelli
Thyago Marsicano Vieira
Washington Silva Noguera
Davy Carlos Mendes Rapozo
Marcus André Acioly
Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1
Cancer Medicine
malignant peripheral nerve sheath tumor
mast cell
mast cell density
microvascular density
neoangiogenesis
neurofibromatosis type 1
title Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1
title_full Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1
title_fullStr Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1
title_full_unstemmed Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1
title_short Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1
title_sort prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1
topic malignant peripheral nerve sheath tumor
mast cell
mast cell density
microvascular density
neoangiogenesis
neurofibromatosis type 1
url https://doi.org/10.1002/cam4.1977
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