International Journal of Urology (2005) 12, 563–569 Blackwell Science, LtdOxford, UKIJUInternational Journal of Urology0919-81722005 Blackwell Publishing Asia Pty LtdMay 2005125563569Original Article Bcl-2 protein and DNA ploidy in renal cell carcinomaA Skolarikos et al. Correspondence: Skolarikos Andreas MD PhD, Sismanoglio Hospital, 6, Laskareos st, Nea Zoi, Peristeri 12137, Athens, Greece. Email: andskol@yahoo.com Received 2 February 2004; accepted 28 October 2004. Original Article Bcl-2 protein and DNA ploidy in renal cell carcinoma: Do they affect patient prognosis? ANDREAS SKOLARIKOS, 1 GERASIMOS ALIVIZATOS, 1 ARISTOTELIS BAMIAS, 3 DIONYSIOS MITROPOULOS, 2 NIKOLAOS FERAKIS, 1 CHARALAMPOS DELIVELIOTIS 1 AND MELETIOS-ATHANASIOS DIMOPOULOS 3 2 First and 1 Second Departments of Urology and Department of 3 Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece Abstract Aim: The aim of the present study was to correlate bcl-2 protein expression and DNA-ploidy status with established prognostic parameters in renal cell carcinoma (RCC) and to examine their impact on disease progression and patient survival. Methods: Both parameters were prospectively measured in 50 consecutive radical nephrectomy specimens using flow cytometry. They were correlated with the tumor grade, stage and histological type. Kaplan-Meier survival analysis for all parameters was performed. Results: Bcl-2 protein expression was higher in RCC compared to normal renal tissue (P < 0.0001). Aneuploid tumors had higher bcl-2 expression compared to diploid tumors (P = 0.015). Bcl-2 expression and DNA content were not correlated with tumor histological types (P = 0.277/ P = 0.419), grades (P = 0.690/P = 0.449), T categories (P = 0.637/P = 0.585) or stages (P = 0.726/ P = 0.800). Median follow-up time was 46 months (range, 5–84) with a mean overall survival of 61.8 months (95% confidence interval, 53.7–69.9). Tumor stage was the only statistically important prognostic factor (P = 0.0045). Conclusion: Although Bcl-2 expression was correlated with tumor DNA content, the prognostic value of these two parameters following radical nephrectomy was not established. Key words bcl-2, DNA ploidy, prognosis, renal cell carcinoma. Introduction Renal cell carcinomas (RCC) are heterogeneous tumors that include several distinct entities with a range of biological and clinical behaviors, from relatively favor- able to extremely aggressive. The heterogeneity leads to unpredictable outcome and survival. 1 The clinical, radiological and pathological features of RCC provide important prognostic information. 1 However, these mea- sures do not take into consideration the molecular- biological features of the tumor. Individual patients with a different tumor stage and/or grade may have a similar survival; this could be due to different tumor cytogenic and molecular characteristics among patients with sim- ilar stages and grades. 1 Various investigators have reported the role of biomolecular indices and oncogenes as potential prognostic parameters. 1 The bcl-2 family of genes includes critical regulators of the programmed cell death pathway. The expression of these genes is frequently altered in human cancers, thus contributing to neoplastic cell expansion by pro- longing cell survival. 2 The first identified member of this gene family, bcl-2, was discovered through its in- volvement in t (14; 18) chromosomal translocations commonly found in lymphomas. 3 Since then, over- expression of bcl-2 has been reported in a wide variety of cancers, including prostate, colorectal, lung, renal and other types of solid tumors and leukemias. 4 Many studies have tried to link the expression of these genes with patient prognosis. 4,5 A variety of experiments pro-