Astrocitoma pilocítico em adultos: estudo histopatológico, imuno-histoquímico e molecular com correlação clínico-patológica
Data
2022
Autores
Marcos, Débora Salles 
Orientadores
Stávale, João Norberto
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: Os astrocitomas pilocíticos são os tumores primários do SNC mais encontrados em crianças e adolescentes, sendo raros em indivíduos adultos. Enquanto alguns autores relatam ter encontrado um prognóstico favorável quando o tumor é encontrado na faixa etária adulta, outros o associaram a uma maior mortalidade. A alteração molecular mais observada em casos de astrocitoma pilocítico no grupo pediátrico é a fusão gênica BRAF-KIAA1549, e ainda existem poucos estudos que confirmem a presença desta fusão na população adulta. Objetivo: Este estudo se propôs a investigar a presença de fusões do gene BRAF na região 7q34 em indivíduos adultos com astrocitoma pilocítico, além de identificar a expressão imuno-histoquímica de BRAFV600E, associando estes achados aos histopatológicos e clínicos. Métodos: Foi realizado um levantamento bibliográfico que culminou nos Capítulos I, II e III, que abordam as principais informações acerca do tumor e seu desenvolvimento. A partir disso, seguiu-se um estudo retrospectivo contido no Capítulo IV, relativo a 21 pacientes com idade superior a 18 anos com diagnóstico de astrocitoma pilocítico. As amostras foram selecionadas após análise de materiais dos anos de 1991 a 2015, provenientes do arquivo do Departamento de Patologia da UNIFESP, e submetidos à revisão histopatológica, exame imuno-histoquímico e FISH. Resultados: Através da avaliação da imunorreatividade de BRAFV600E, 29% dos casos foram classificados como grupo 1, 57% como grupo 2
e 14% como grupo 3, sendo considerados como positivos apenas os grupos 2 e 3. Na análise por FISH encontrou-se a fusão BRAF-KIAA1549 em apenas um caso, enquanto em outros dois foram encontradas deleções referentes à fusão FAM131B-BRAF. Conclusão: Os casos considerados positivos para a imunorreatividade de BRAFV600E potencialmente podem ser tratados com inibidores de BRAF, enquanto para os casos negativos é necessário realizar uma confirmação diagnóstica através de técnicas moleculares para escolher o tratamento adequado. Em relação às fusões gênicas, sugere-se que a presença da variante FAM131B-BRAF possa ser mais significativa nestes indivíduos. Até onde sabemos, este é o primeiro estudo brasileiro que objetivou investigar as possíveis alterações genéticas no gene BRAF em astrocitomas pilocíticos, especificamente em indivíduos adultos. Apenas 1 paciente veio a óbito, porém por complicações operatórias e não pela doença em si, sugerindo uma boa evolução destes indivíduos. Por fim, propõem-se novos estudos que investiguem outros genes e suas alterações, bem como novas propostas de marcadores imuno-histoquímicos que sejam relevantes.
Introduction: Pilocytic astrocytomas are the most common CNS primary tumors in children and adolescents, being rare in adults. While some authors report a favorable prognosis when the tumor is found in the adult age group, others have associated it with higher mortality. The molecular alteration most observed in cases of pilocytic astrocytoma in the pediatric group is the BRAF-KIAA1549 gene fusion, and there are still few studies confirming the presence of this fusion in the adult population. Objective: This study aimed to investigate the presence of BRAF gene fusions in the 7q34 region in adults with pilocytic astrocytoma, in addition to identifying the immunohistochemical expression of BRAFV600E, associating these findings with histopathological and clinical ones. Methods: A bibliographic research culminated in Chapters I, II and III, which address the main information about the tumor and its development. From this, a retrospective study contained in Chapter IV concerns 21 patients aged over 18 years with a diagnosis of pilocytic astrocytoma. The samples were selected after analysis of materials from 1991 to 2015, of the Department of Pathology at UNIFESP, and submitted to histopathological review, immunohistochemical examination and FISH. Results: Through the evaluation of BRAFV600E immunoreactivity, 29% of the cases were classified as group 1, 57% as group 2 and 14% as group 3, with only groups 2 and 3 being considered positive. The BRAF-KIAA1549 fusion was found in only one case, while deletions related to the FAM131B-BRAF fusion were found in two others. Conclusion: Cases considered positive for BRAFV600E immunoreactivity can potentially be treated with BRAF inhibitors, while negative cases require diagnostic confirmation using molecular techniques to choose the appropriate treatment. Regarding gene fusions, it is suggested that the presence of the FAM131B-BRAF variant may be more significant in these individuals. To the best of our knowledge, this is the first Brazilian study that aimed to identify the mutation and gene fusion most commonly found in pilocytic astrocytomas, specifically in adults. Only 1 patient died, but due to operative complications and not the disease itself, suggesting a good evolution of these individuals. Finally, new studies are proposed that investigate other genes and their alterations, as well as new proposals for relevant immunohistochemical markers.
Introduction: Pilocytic astrocytomas are the most common CNS primary tumors in children and adolescents, being rare in adults. While some authors report a favorable prognosis when the tumor is found in the adult age group, others have associated it with higher mortality. The molecular alteration most observed in cases of pilocytic astrocytoma in the pediatric group is the BRAF-KIAA1549 gene fusion, and there are still few studies confirming the presence of this fusion in the adult population. Objective: This study aimed to investigate the presence of BRAF gene fusions in the 7q34 region in adults with pilocytic astrocytoma, in addition to identifying the immunohistochemical expression of BRAFV600E, associating these findings with histopathological and clinical ones. Methods: A bibliographic research culminated in Chapters I, II and III, which address the main information about the tumor and its development. From this, a retrospective study contained in Chapter IV concerns 21 patients aged over 18 years with a diagnosis of pilocytic astrocytoma. The samples were selected after analysis of materials from 1991 to 2015, of the Department of Pathology at UNIFESP, and submitted to histopathological review, immunohistochemical examination and FISH. Results: Through the evaluation of BRAFV600E immunoreactivity, 29% of the cases were classified as group 1, 57% as group 2 and 14% as group 3, with only groups 2 and 3 being considered positive. The BRAF-KIAA1549 fusion was found in only one case, while deletions related to the FAM131B-BRAF fusion were found in two others. Conclusion: Cases considered positive for BRAFV600E immunoreactivity can potentially be treated with BRAF inhibitors, while negative cases require diagnostic confirmation using molecular techniques to choose the appropriate treatment. Regarding gene fusions, it is suggested that the presence of the FAM131B-BRAF variant may be more significant in these individuals. To the best of our knowledge, this is the first Brazilian study that aimed to identify the mutation and gene fusion most commonly found in pilocytic astrocytomas, specifically in adults. Only 1 patient died, but due to operative complications and not the disease itself, suggesting a good evolution of these individuals. Finally, new studies are proposed that investigate other genes and their alterations, as well as new proposals for relevant immunohistochemical markers.