RESUMO
Over the last decade several genetic alterations involved in the pathogenesis and progression of renal cell carcinoma have been identified. These findings will have a wide implication for the diagnosis and management of renal cell carcinomas. This review provides a discussion of general principles of tumor development as well as the specific mechanisms underlying renal carcinogenesis.
Assuntos
Carcinoma de Células Renais/genética , Aberrações Cromossômicas , Neoplasias Renais/genética , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Reparo do DNA/genética , Genes Supressores , Marcadores Genéticos/genética , Humanos , Rim/patologia , Neoplasias Renais/classificação , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Oncogenes/genética , Fatores de RiscoRESUMO
PURPOSE: We identified novel biological markers of prognosis in primary histopathological specimens from patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Apoptotic indexes (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling), proliferation rates (Ki-67 antigen), p21 (WAF1/cip1) expression and CD95 (APO-1/Fas) expression were determined in paraffin embedded nephrectomy specimens from 73 patients with histologically confirmed, progressive metastatic disease. Kaplan-Meier survival analysis, log rank statistics and 2-proportional Cox regression analysis were done to identify new risk factors in addition to conventional classification criteria, and demonstrate statistical independence. RESULTS: Multivariate analysis indicated that primary tumor apoptosis (p = 0.0116) and the interval from diagnosis to metastatic disease (p = 0.002) had a high predictive impact on overall survival after initial diagnosis. Patients were assigned to 2 risk groups, namely a poor prognosis group with a median survival of 20 months, defined by apoptosis less than 6% in the primary tumor nephrectomy specimen and a time from initial diagnosis to metastatic disease of less than 6 months, and a good prognosis group with a median survival of 56 months, defined as the absence of 1 or 2 risk factors. CONCLUSIONS: Our findings showed that primary tumor apoptosis is a novel independent predictor in patients with metastatic renal cell carcinoma at initial diagnosis. It leads to a new prognostic index in the pretreatment classification of metastatic renal cell carcinoma.
