O valor prognóstico e diagnóstico da imunomarcação de Ki- 67, p53, MDM2, MGMT, Caspase-3 clivada e da amplificação gênica EGFR no glioblastoma, astrocitoma difuso e astrocitoma anaplásico

• Ano de defesa: 2011
• Autor(a) principal: Andrade, Cecília Vianna de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Programa de Pós-graduação em Patologia; Patologia
• Palavras-chave em Português: Neoplassia; Glioma; Fatores prognósticos; Astrocitoma; Glioblastoma; Imuno-histoquímica; Marcadores prognósticos; Hibridização in situ cromogênica (CISH); EGFR; MEDICINA; PATOLOGIA GERAL; Astrocytoma; Prognostic factors; In situ hybridization (CISH); CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
• Link de acesso: https://app.uff.br/riuff/handle/1/19410

The astrocytic tumors are the most frequent intracranial primary tumors; glioblastoma is the most common and has the worst prognosis. The recognition of molecular changes related to the oncogenic pathways of diffuse astrocytomas (DA), anaplastic astrocytoma (AA) and glioblastoma (GBM) is extremely important for better therapeutic approach, identification of prognostic markers and to define the necessity of incorporating molecular studies in routine diagnosis, as is already known for breast cancer. These changes may vary and have different impact on various populations, with few reports published about the molecular profile of the Brazilian population. The aim of this study was to quantify the immunolabeling of antibodies to EGFR, p53, MDM2, MGMT, Ki-67, cleaved caspase-3, in DA, AA and GBM to identify their immunohistochemical profile; to assess EGFR gene amplification; to evaluate whether the immunohistochemical study of EGFR would be a useful screening method for chromogenic in situ hybridization for EGFR; to check whether there is correlation between the various immunostainings themselves and with the survival time to evaluate their prognostic relevance; to identify whether there is correlation between the immunohistochemical findings and sex, age and histological type, and to standardize a routine analysis for the DA, AA and GBM with diagnostic and prognostic relevance. We reviewed the medical records and the slides of cases diagnosed as DA, AA and GBM, from 1989 to 2007, in the Neuropathology Division, Pathology Service, Department of Pathology, University Hospital Antônio Pedro, Fluminense Federal University, and from 1997 to 2007, in the Pathology Division, National Cancer Institute. The immunohistochemical and in situ hybridization methods were performed using the technique "Tissue Micro Array (TMA), assembled from paraffin blocks. It was verified that EGFR overexpression (score 3) and EGFR amplification, were related to the diagnosis of GBM and age above 50 years, while the focal amplification was identified in DA and AA; the other markers did not correlate with diagnosis or age; Ki-67 above 5% in DA, as well as immunostaining for p53 (above 10%) allowed the identification of a subgroup with lower survival; the histological diagnosis and the age were the most significant prognostic factors in all forms of statistical analysis performed. We concluded that the immunohistochemical technique for the EGFR may be useful in the diagnostic evaluation, but not as a screening method for in situ hybridization for EGFR; the correlations between the various immunohistochemical markers did not define a diagnostic and prognostic profile; we do not recommend the routine use of CISH because of its high cost and little diagnostic information; the antibodies KI-67 and p53 demonstrated prognostic value for cases diagnosed as DA and GBM, respectively, but the histological diagnosis and the age were the most relevant prognostic markers; the other markers were not useful for the diagnosis or prognosis; the results of this study confirmed the need of further studies on molecular genetics.