ALLELIC LOSS ON CHROMOSOMES 8 AND 9 CORRELATES WITH CLINICAL OUTCOME IN LOCALLY ADVANCED CLEAR CELL CARCINOMA OF THE KIDNEY

Abstract

We correlated allelic loss on chromosomes 8p, 9p and 14q with clinical outcome in locally advanced conventional renal cell carcinoma. We analyzed radical nephrectomy specimens from 72 stage P3N0 conventional renal cell carcinomas by microsatellite loss of heterozygosity (LOH) analyses directed at chromosomes 3p, 8p, 9p and 14q (2 primers per chromosome). All patients were treated with surgery only. LOH results were correlated with disease-free survival using the Kaplan-Meier method. We detected LOH on chromosome 3p in 60 of 64 (94%), on chromosome 8p in 19 of 59 (32%), on 9p in 21 of 67 (31%) and on 14q in 18 of 70 (26%) informative cases. Of the 72 patients 24 (33%) had recurrence during followup. On univariate analysis patients with tumors demonstrating LOH on chromosomes 8p and 9q were at high risk for recurrence (p = 0.01). The correlation of recurrence with LOH approached significance for the individual chromosomes 8p and 9p (p = 0.10 and 0.14, respectively). No correlation was observed of LOH on chromosome 14q with recurrence (p = 0.42). The correlation of tumor grade with risk of relapse also approached significance (p = 0.12). On multivariate analysis LOH on chromosome 8p was a more powerful predictor of recurrence than tumor grade. When combinations of LOH on chromosomes were tested, LOH on chromosomes 8p and 9p was the most powerful predictor of recurrence (p = 0.006). LOH on chromosomes 8p or 9p may provide prognostic significance in patients with locally advanced renal cell carcinoma.