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p53 expression and subcellular survivin localization improve the diagnosis and prognosis of patients with diffuse astrocytic tumors

Authors
  • Faccion, Roberta Soares1, 2
  • Bernardo, Paula Sabbo1, 3
  • de Lopes, Giselle Pinto Faria1
  • Bastos, Leonardo Soares4
  • Teixeira, Cristina Lordello5
  • de Oliveira, José Antonio6
  • Fernandes, Priscila Valverde7
  • Dubois, Luiz Gustavo8
  • Chimelli, Leila9
  • Maia, Raquel Ciuvalschi1
  • 1 Hospital do Câncer I, Centro de Pesquisas do Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Praça da Cruz Vermelha 23/6° andar, Rio de Janeiro, 20230-130, Brazil , Rio de Janeiro (Brazil)
  • 2 Universidade Federal do Rio de Janeiro, Programa de Pós-Graduação em Ciências Biológicas – Fisiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Rio de Janeiro, Brazil , Rio de Janeiro (Brazil)
  • 3 Programa de Pós-Graduação Stricto Sensu em Oncologia, INCA, Rio de Janeiro, Brazil , Rio de Janeiro (Brazil)
  • 4 Programa de Computação Científica (PROCC), Presidência, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil , Rio de Janeiro (Brazil)
  • 5 Serviço de Patologia Clínica, Hospital do Câncer I, INCA, Rio de Janeiro, Brazil , Rio de Janeiro (Brazil)
  • 6 Serviço de Neurocirurgia, INCA, Rio de Janeiro, Brazil , Rio de Janeiro (Brazil)
  • 7 Divisão de Patologia, INCA, Rio de Janeiro, Brazil , Rio de Janeiro (Brazil)
  • 8 Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Laboratório de Biomedicina do Cérebro, Rio de Janeiro, Brazil , Rio de Janeiro (Brazil)
  • 9 Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Laboratório de Neuropatologia e Genética Molecular, Rio de Janeiro, Brazil , Rio de Janeiro (Brazil)
Type
Published Article
Journal
Cellular Oncology
Publisher
Springer-Verlag
Publication Date
Jan 26, 2018
Volume
41
Issue
2
Pages
141–157
Identifiers
DOI: 10.1007/s13402-017-0361-5
Source
Springer Nature
Keywords
License
Yellow

Abstract

PurposeDiffuse astrocytic tumors are the most frequently occurring primary central nervous system (CNS) tumors. Their histological sub-classification into diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GB) is challenging and the available prognostic factors are limited to age and tumor subtype. Biomarkers that may improve the histological sub-classification and/or serve as prognostic factors are, therefore, urgently needed. The relationship between survivin and p53 in diffuse astrocytic tumor progression and survival is currently unclear. Here, we aimed to assess the relevance of these proteins in the accuracy of the histological sub-classification of these tumors and their respective treatment responses.MethodsOne hundred and thirty-three formalin-fixed paraffin-embedded diffuse astrocytic tumor samples were included. The tumor samples were histologically reviewed and subsequently assessed for p53 and survivin expression and the presence of the IDH R132H mutation by immunohistochemistry. p53 expression levels and survivin subcellular localization patterns were correlated with histological classification and clinical outcome.ResultsWe found that age and histological subtype were the only features with a prognostic impact. In addition, we found that high p53 expression levels and a nuclear survivin localization correlated with the AA subtype, whereas cytoplasmic survivin localization correlated with the GB subtype. We also found that patients carrying tumors with a high cytoplasmic survivin expression, a high nuclear survivin expression or a high p53 expression, and who did not receive radiotherapy, exhibited poorer short-term and long-term overall survival rates.ConclusionsOur data suggest that subcellular survivin localization and p53 expression may be employed as valuable tools to improve the accuracy of the histological sub-classification of diffuse astrocytic tumors. Patients whose tumors overexpress these proteins may benefit from radiotherapy, irrespective age and/or histological classification.

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