Roberta Soares Faccion1,2, Paula Sabbo Bernardo1,3, Giselle Pinto Faria de Lopes1, Leonardo Soares Bastos4, Cristina Lordello Teixeira5, José Antonio de Oliveira6, Priscila Valverde Fernandes7, Luiz Gustavo Dubois8, Leila Chimelli9, Raquel Ciuvalschi Maia10. 1. Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Hospital do Câncer I, Centro de Pesquisas do Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), Praça da Cruz Vermelha 23/6° andar, Rio de Janeiro, 20230-130, Brazil. 2. Programa de Pós-Graduação em Ciências Biológicas - Fisiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 3. Programa de Pós-Graduação Stricto Sensu em Oncologia, INCA, Rio de Janeiro, Brazil. 4. Programa de Computação Científica (PROCC), Presidência, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. 5. Serviço de Patologia Clínica, Hospital do Câncer I, INCA, Rio de Janeiro, Brazil. 6. Serviço de Neurocirurgia, INCA, Rio de Janeiro, Brazil. 7. Divisão de Patologia, INCA, Rio de Janeiro, Brazil. 8. Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil. 9. Laboratório de Neuropatologia e Genética Molecular, Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil. 10. Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Hospital do Câncer I, Centro de Pesquisas do Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), Praça da Cruz Vermelha 23/6° andar, Rio de Janeiro, 20230-130, Brazil. rcmaia@inca.gov.br.
Abstract
PURPOSE: Diffuse 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. METHODS: One 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. RESULTS: We 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. CONCLUSIONS: Our 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.
PURPOSE: Diffuse 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. METHODS: One 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. RESULTS: We 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. CONCLUSIONS: Our 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.
Authors: David N Louis; Arie Perry; Guido Reifenberger; Andreas von Deimling; Dominique Figarella-Branger; Webster K Cavenee; Hiroko Ohgaki; Otmar D Wiestler; Paul Kleihues; David W Ellison Journal: Acta Neuropathol Date: 2016-05-09 Impact factor: 17.088
Authors: Young-Ho Kim; Sumihito Nobusawa; Michel Mittelbronn; Werner Paulus; Benjamin Brokinkel; Kathy Keyvani; Ulrich Sure; Karsten Wrede; Yoichi Nakazato; Yuko Tanaka; Anne Vital; Luigi Mariani; Robert Stawski; Takuya Watanabe; Umberto De Girolami; Paul Kleihues; Hiroko Ohgaki Journal: Am J Pathol Date: 2010-11-12 Impact factor: 5.770
Authors: Matthew D Cykowski; Richard A Allen; Angela C Kanaly; Kar-Ming Fung; Roxanne Marshall; Arie Perry; Ethan D Stolzenberg; S Terence Dunn Journal: J Neurooncol Date: 2013-09-21 Impact factor: 4.506