Comparison of positivity frequency of bcl-2 expression in prostate adenocarcinoma with low and high Gleason score

CONTEXT: Multiple genetic and epigenetic factors have been implicated in the oncogenesis and progression of prostate cancer. The major difficulty is in that the clinical management stems from the reality that reliable and accurate prognostic biomarkers are not available and that effective treatment regimens forming hormone-resistant prostate cancers are yet to be developed. Among the most important regulators of apoptosis and programmed cell death is the bcl-2 gene and its related proteins. Elevated levels of bcl-2 protein may contribute to the progression of prostate cancers to a metastatic and hormone-insensitive state characterized by poor responses to chemotherapy. OBJECTIVE: To characterize the expression of bcl-2 proteins as a prognostic factor in humans. DESIGN: A retrospective approach. SETTING: Urology section, Federal University of São Paulo. DIAGNOSTIC TEST USED: Immunohistochemical analysis using bcl-2 protein antibody and normal staining by hematoxylin-eosin. MAIN MEASUREMENTS: Prognostic relations and protein expression were evaluated considering the total sample (28) divided into two groups, high (8 to 10) and low (2 to 4), separated according to the histological differentiation grade (Gleason score) with 10 and 18 samples, respectively. RESULTS: The differentiation of grade into two groups separated according to the Gleason score in low and high types presented different bcl-2 expression (P < 0.001). CONCLUSION: The higher frequency of bcl-2 immunostaining in tumor samples was observed in association with more advanced Gleason scores and suggests that an increase in the ratio of this anti-apoptotic protein often occurs during progression of prostate cancers.CONTEXTO: Diversos fatores genéticos e ambientais têm sido relacionados à oncogênese e progressão do câncer de próstata. A principal dificuldade na conduta clínica frente a esses tumores consiste no fato de não existirem marcadores prognósticos precisos, e que tratamentos eficazes dos tumores hormônio-resistentes não estão ainda disponíveis. Entre os reguladores mais importantes para avaliar a taxa de apoptose, destaca-se a expressão da proteína bcl-2. Os níveis elevados dessa proteína podem contribuir na progressão dos tumores prostáticos para um estado metastático e/ou hormônio independente, que caracteristicamente não apresenta resposta satisfatória ao tratamento quimioterápico. OBJETIVO: Investigar a expressão da proteína bcl-2 como fator prognóstico em portadores de tumores prostáticos. TIPO DE ESTUDO: Estudo retrospectivo. LOCAL: Disciplina de Urologia da Universidade Federal de São Paulo (UNIFESP). TESTE DIAGNÓSTICO: Exame anatomopatológico convencional por hematoxilina-eosina (HE) e imunohistoquímico. VARIÁVEIS ESTUDADAS: Expressão prognóstica da proteína bcl-2, por técnica imunohistoquímica em portadores de adenocarcinoma da próstata submetidos a prostatectomia radical. AMOSTRA: 28 amostras de tumores de próstata fixadas em parafina, provenientes de pacientes submetidos à prostatectomia radical sem ablação androgênica prévia, avaliadas por HE e por imunohistoquímica para a caracterização da expressão da proteína bcl-2. A expressão foi correlacionada ao grau de diferenciação do tumor, dividindo-se os tumores em dois grupos, segundo o escore de Gleason, em baixo (escore 2 a 4), e alto grau (8 a 10), sendo que os grupos foram divididos em 18 e 10 pacientes, respectivamente. RESULTADOS: Observou-se associação estatisticamente significativa (P < 0, 001) entre expressão elevada da proteína e os casos que apresentavam um escore de Gleason mais elevado (83, 3%), enquanto que no grupo de escore de baixo grau não foi detectada expressão da bcl-2 em 90% das amostras. CONCLUSÕES: O aumento na expressão da proteína bcl-2 em tumores de próstata com escore de Gleason elevado pode estar associado à progressão do adenocarcinoma de próstata.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of SurgeryUNIFESP, EPM, Department of SurgerySciEL

Comparison of positivity frequency of bcl-2 expression in prostate adenocarcinoma with low and high Gleason score

CONTEXT: Multiple genetic and epigenetic factors have been implicated in the oncogenesis and progression of prostate cancer. The major difficulty is in that the clinical management stems from the reality that reliable and accurate prognostic biomarkers are not available and that effective treatment regimens forming hormone-resistant prostate cancers are yet to be developed. Among the most important regulators of apoptosis and programmed cell death is the bcl-2 gene and its related proteins. Elevated levels of bcl-2 protein may contribute to the progression of prostate cancers to a metastatic and hormone-insensitive state characterized by poor responses to chemotherapy. OBJECTIVE: To characterize the expression of bcl-2 proteins as a prognostic factor in humans. DESIGN: A retrospective approach. SETTING: Urology section, Federal University of São Paulo. DIAGNOSTIC TEST USED: Immunohistochemical analysis using bcl-2 protein antibody and normal staining by hematoxylin-eosin. MAIN MEASUREMENTS: Prognostic relations and protein expression were evaluated considering the total sample (28) divided into two groups, high (8 to 10) and low (2 to 4), separated according to the histological differentiation grade (Gleason score) with 10 and 18 samples, respectively. RESULTS: The differentiation of grade into two groups separated according to the Gleason score in low and high types presented different bcl-2 expression (P < 0.001). CONCLUSION: The higher frequency of bcl-2 immunostaining in tumor samples was observed in association with more advanced Gleason scores and suggests that an increase in the ratio of this anti-apoptotic protein often occurs during progression of prostate cancers