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A Clinicopathologic Study on the Role of Estrogen, Progesterone, and Their Classical and Nonclassical Receptors in Cutaneous Neurofibromas of Individuals With Neurofibromatosis 1.

Authors
  • Rozza-de-Menezes, Rafaela E1, 2, 3
  • Almeida, Lilian M1, 2
  • Andrade-Losso, Raquel M1, 2
  • de Souza Vieira, Gustavo1, 2
  • Siqueira, Orlando H K4
  • Brum, Carolina I5
  • Riccardi, Vincent M6
  • Cunha, Karin S1, 2, 3
  • 1 Graduate Program in Pathology, School of Medicine.
  • 2 Department of Pathology, School of Medicine, Antonio Pedro University Hospital.
  • 3 Department of General and Specialized Surgery, School of Medicine, Universidade Federal Fluminense, Niterói, Brazil. , (Brazil)
  • 4 Neurofibromatosis National Center (Centro Nacional de Neurofibromatose), Rio de Janeiro, Brazil. , (Brazil)
  • 5 Department of Pathology, School of Medicine, Universidade Federal de Goiás, Goiânia, Brazil. , (Brazil)
  • 6 The Neurofibromatosis Institute, La Crescenta, CA.
Type
Published Article
Journal
American Journal of Clinical Pathology
Publisher
Oxford University Press
Publication Date
Dec 08, 2020
Identifiers
DOI: 10.1093/ajcp/aqaa186
PMID: 33289020
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To evaluate the expression of progesterone receptor (PR), estrogen receptor (ER), and G protein-coupled estrogen receptor 1 (GPER-1) in cutaneous neurofibromas (cNFs) and their correlation with demographic, clinical, and laboratory data of individuals with neurofibromatosis 1 (NF1). The association of PROGINS polymorphism and PR expression in cNFs, as well as the serum steroidal hormones and the number of cNFs, was investigated. The sample comprised 80 large and 80 small cNFs from 80 individuals with NF1. PR, ER, GPER-1, and Ki-67 expression were investigated by immunohistochemistry in tissue micro- and macroarrays and quantified using a digital computer-assisted method. The number of cNFs, the levels of serum 17β estradiol and progesterone, and the PROGINS polymorphism were identified. Twelve (8.5%) small cNFs were weakly positive for ER, 131 (92.3%) cNFs expressed PR, and all (100%) cNFs expressed GPER-1. Large cNFs showed a higher expression of PR (P < .0001) and GPER-1 (P = .019) and had a higher intensity of staining for these receptors (P < .0001). The cell proliferation index was positively correlated with PR (P = .001). Persons with more cNFs had higher serum levels of progesterone (P = .001). These findings emphasize the role of estrogen and progesterone in cNF development and suggest that these hormones may act on cNF cells via a noncanonical pathway through GPER-1. © American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: [email protected]

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