Differential expression in clear cell renal cell carcinoma identified by gene expression profiling

Abstract

PURPOSE: Gene expression profiling has been shown to provide prognostic information on patients with solitary sporadic renal cell carcinoma. To our knowledge there is no reliable way to differentiate synchronous renal metastasis from bilateral primary tumors in patients with bilateral renal cell carcinoma. We present data using a custom kidney cancer cDNA array that can predict the outcome in patients with unilateral and bilateral renal cell carcinoma.

MATERIALS AND METHODS: Fresh frozen tissue from 38 clear cell renal cell carcinomas was analyzed using a cancer cDNA array containing 3,966 genes relevant to cancer or kidney development. Median followup was 5.3 years. Cancer recurred in 12 patients (43%) and 11 (39%) had died by the last followup.

RESULTS: Using a training data set of 8 tumors a 44 gene expression profile distinguishing aggressive and indolent clear cell renal cell carcinoma was identified. Of 29 single clear cell renal cell carcinomas 16 and 13 were predicted to be indolent and aggressive, respectively, by the gene expression profile. Recurrence-free survival at 5 years was 68% and 42% in these 2 groups, respectively (p = 0.032). Clear cell renal cell carcinoma classified as indolent or aggressive according to SSIGN (stage, size, grade and necrosis) score showed a 5-year recurrence-free survival rate of 78% and 42%, respectively (p = 0.021). On Cox proportional hazards analysis the gene expression profile was not an independent predictor of recurrence-free survival after accounting for SSIGN score. Gene expression profile classification correlated with cancer specific survival at 5 years in 4 of 4 patients with metachronous clear cell renal cell carcinoma but in only 2 of 4 with bilateral synchronous clear cell renal cell carcinoma.

CONCLUSIONS: Gene expression profiling using a kidney cancer relevant cDNA array can differentiate between aggressive and indolent clear cell renal cell carcinomas. Gene expression profile results may be most useful for unilateral clear cell renal cell carcinoma when results are discordant with predictions of tumor behavior based on standard clinicopathological features. In addition, gene expression profiling can provide prognostic information that may help characterize tumors of unknown clinical stage, such as bilateral metachronous clear cell renal cell carcinoma.