Search

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. 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. 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. 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.

Astrocytomas are the most frequent subtype of primary central nervous system (CNS) tumors. Diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III) and glioblastoma (GB–grade IV) are diffuse infiltrating astrocytomas derived from glial cells or precursors. Despite continuous efforts from the scientific community, these tumors still have a poor prognosis. Histologic grading is still challenging, and prognostic factors are still limited to age and tumor grade. Biomarkers that could improve histologic grading, especially that could help differentiate grade III from the other subtypes, and/or serve as prognostic factors are much needed. Furthermore, the relationship between survivin and p53 in astrocytoma progression and survival is still controversial. The present study aims to investigate the role of these proteins in the accuracy of histologic grading of diffuse astrocytic tumors and treatment response. One hundred thirty-five formalin-fixed, paraffin-embedded astrocytoma samples were obtained from patients. Tumor samples were reviewed and stained for survivin and p53 by immunohistochemistry, and the staining levels and survivin subcellular localization were correlated with histologic grading and patient outcomes. Age and histologic grade were the only clinical features that had a prognostic impact. High nuclear survivin and p53 correlated with grade III astrocytomas. High cytoplasmic survivin correlated with GB. Furthermore, patients whose tumors expressed high cytoplasmic survivin, high nuclear surviving, or high p53 and did not receive radiotherapy had worse short-term and long-term survival. Our results suggest that survivin subcellular localization and p53 expression improve the accuracy of histologic grading. Patients whose tumors overexpress these proteins benefit from radiotherapy regardless of age and histologic grade. Furthermore, patients whose tumors overexpress survivin may benefit from novel targeted antisurvivin treatment. Citation Format: Roberta Soares Faccion*, Paula Sabbo Bernardo*, Giselle Pinto de Faria Lopes*, Leonardo Soares Bastos, Cristina Lordello Teixeira, José Antonio de Oliveira, Priscila Valverde Fernades, Luiz Gustavo Dubois, Leila Maria Chimelli, Raquel Ciuvalschi Maia. P53 expression and survivin subcellular localization contribute to the diagnosis and prognosis of patients with astrocytomas [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B66.