Correlação entre ressonância magnética, expressão do Ki-67 e p53, e prognóstico em astrocitomas

Resumo

Objetivos Avaliar a correlação entre a expressão do Ki-67 e do p53 em astrocitomas graus II a IV, as características da RM e seu prognóstico.

Métodos e Resultados Este é um estudo longitudinal retrospectivo do tipo coorte histórico que avaliou 45 pacientes. O prognóstico foi avaliado mediante revisão dos prontuários. A avaliação imuno-histoquímica foi realizada no Serviço de Patologia do HB. A avaliação das imagens de RM foi feita no Serviço de Radiologia. A sobrevida média dos pacientes foi de 581,4 dias no grau IV; 1.704,8 dias no grau III; e 1.044,8 dias no grau II. Para cada grau, os seguintes percentuais de células positivas de Ki-67 e p53 tiveram respectivamente: 97,8 e 80% de positividade no grau IV; 72,7 e 73,4% de positividade no grau III; e 70 e 80% de positividade no grau II. Observou-se diferença estatística na expressão de Ki-67 entre os graus III e IV (P = 0,014). A RM mostrou especificidade de 64% e sensibilidade de 100% para a presença de necrose tumoral.

Conclusão Concluímos que a análise da positividade do Ki-67 e do p53 não permite sua correlação com a sobrevida dos pacientes, apesar de ambos terem sua frequência distribuída de maneira semelhante. A RM tem especificidade moderada em relação ao exame patológico.

Abstract

Objectives To evaluate the correlation between the expression of Ki -67 and p53 in astrocytomas grades II to IV, the characteristics of MRI and its prognosis.

Methods This was a retrospective longitudinal cohort study of its kind that evaluated 45 patients. Prognosis was assessed by review of medical records. The immunohistochemical evaluation was performed at the Pathology Service of HB. The evaluation of MRI images was taken in the Radiology Department. The median survival of patients was 581.4 days in grade IV; 1704.8 days in grade III; 1044.8 days in grade II. For each grade, the following percentages of cells positive for Ki -67 and p53 , respectively : 97.8% and 80% had a positive grade IV ; 72.7% and 73.4% positivity in grade III ; 70% and 80% in stage II positivity . There was statistical difference in Ki -67 between grades III and IV (P = 0.014). MRI showed 64% specificity and 100% sensitivity for the presence of tumor necrosis.

Conclusion We conclude that the analysis of the positivity of Ki -67 and p53 expression does not allow correlation with patient survival, although both their frequency distributed similarly. MRI has moderate specificity in relation to pathological examination.

Palavras-Chave

astrocitoma - ressonância magnética - antígeno Ki-67 - proteína supressora tumoral p53 - prognóstico

Keywords

astrocytoma - magnetic resonance imaging - Ki-67 antigen - tumor suppressor protein p53 - prognosis

• Referências

• 1 Kleihues P, Louis DN, Scheithauer BW , et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002; 61 (3) 215-225 , discussion 226–229
• 2 Samuels MA. Update in neurology. Ann Intern Med 2007; 146 (2) 128-132
• 3 Mineo JF, Bordron A, Baroncini M , et al. Prognosis factors of survival time in patients with glioblastoma multiforme: a multivariate analysis of 340 patients. Acta Neurochir (Wien) 2007; 149 (3) 245-252 , discussion 252–253
• 4 Hulshof MC, Koot RW, Schimmel EC, Dekker F, Bosch DA, González González D. Prognostic factors in glioblastoma multiforme. 10 years experience of a single institution. Strahlenther Onkol 2001; 177 (6) 283-290
• 5 Johannessen AL, Torp SH. The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas. Pathol Oncol Res 2006; 12 (3) 143-147
• 6 Moskowitz SI, Jin T, Prayson RA. Role of MIB1 in predicting survival in patients with glioblastomas. J Neurooncol 2006; 76 (2) 193-200
• 7 Uematsu M, Ohsawa I, Aokage T , et al. Prognostic significance of the immunohistochemical index of survivin in glioma: a comparative study with the MIB-1 index. J Neurooncol 2005; 72 (3) 231-238
• 8 Kato H, Fujimura M, Kumabe T, Ishioka C, Kanamaru R, Yoshimoto T. PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma. J Clin Neurosci 2004; 11 (1) 37-41
• 9 Faria MHG, Gonçalves BP, do Patrocínio RM, de Moraes-Filho MO, Rabenhorst SHB. Expression of Ki-67, topoisomerase IIalpha and c-MYC in astrocytic tumors: correlation with the histopathological grade and proliferative status. Neuropathology 2006; 26 (6) 519-527
• 10 Lindboe CF, von der Ohe G, Torp SH. Determination of proliferation index in neoplasms using different Ki-67 equivalent antibodies. APMIS 2003; 111 (5) 567-570
• 11 Simmons ML, Lamborn KR, Takahashi M , et al. Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients. Cancer Res 2001; 61 (3) 1122-1128
• 12 Birner P, Piribauer M, Fischer I , et al. Prognostic relevance of p53 protein expression in glioblastoma. Oncol Rep 2002; 9 (4) 703-707
• 13 Shiraishi S, Tada K, Nakamura H , et al. Influence of p53 mutations on prognosis of patients with glioblastoma. Cancer 2002; 95 (2) 249-257
• 14 Lutterbach J, Sauerbrei W, Guttenberger R. Multivariate analysis of prognostic factors in patients with glioblastoma. Strahlenther Onkol 2003; 179 (1) 8-15
• 15 Pope WB, Sayre J, Perlina A, Villablanca JP, Mischel PS, Cloughesy TF. MR imaging correlates of survival in patients with high-grade gliomas. AJNR Am J Neuroradiol 2005; 26 (10) 2466-2474
• 16 Pierallini A, Bonamini M, Pantano P , et al. Radiological assessment of necrosis in glioblastoma: variability and prognostic value. Neuroradiology 1998; 40 (3) 150-153
• 17 Law M, Yang S, Wang H , et al. Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol 2003; 24 (10) 1989-1998
• 18 Plathow C, Lichy MP, Bachert P, Zuna I, Kauczor HU. The role of MRI in patients with astrocytoma WHO II treated with fractionated stereotactic radiotherapy. Eur Radiol 2004; 14 (4) 679-685
• 19 Schlüter C, Duchrow M, Wohlenberg C , et al. The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol 1993; 123 (3) 513-522
• 20 Pinho MSL. Proteína P53: Algum valor clínico ou apenas pesquisa? Uma revisão da literatura. Revista SBCP. Disponível em: http://www.sbcp.org.br/revista/nbr204/P258_260.htm Acessado em 2014 (Abril 12).
• 21 Tortosa A, Viñolas N, Villà S , et al. Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas. Cancer 2003; 97 (4) 1063-1071
• 22 Aldape KD, Okcu MF, Bondy ML, Wrensch M. Molecular epidemiology of glioblastoma. Cancer J 2003; 9 (2) 99-106
• 23 Ribeiro MdeC, Coutinho LMB, Hilbig A. The role of apoptosis, cell proliferation index, bcl-2, and p53 in glioblastoma prognosis. Arq Neuropsiquiatr 2004; 62 (2A): 262-270
• 24 Wu WC, Chen CY, Chung HW, Juan CJ, Hsueh CJ, Gao HW ; Wen – Chu Wu. Discrepant MR spectroscopic and perfusion imaging results in a case of malignant transformation of cerebral glioma. AJNR Am J Neuroradiol 2002; 23 (10) 1775-1778
• 25 Korshunov A, Golanov A, Sycheva R. Immunohistochemical markers for prognosis of cerebral glioblastomas. J Neurooncol 2002; 58 (3) 217-236