Cell cycle progression score to predict metastatic progression of clear cell renal cell carcinoma after resection.

Abstract

442 Background: Clear cell renal cell carcinoma (ccRCC) is primarily treated surgically when organ confined, but requires close follow-up to evaluate for recurrence. Expression levels of cell cycle progression (CCP) genes have prognostic value in certain cancers. We evaluated the prognostic value of the CCP expression in surgically resected ccRCC. Methods: Medical records were retrospectively reviewed. Patients with metastasis or lymph node involvement at surgery were excluded. Cases developed metastasis within 5 years of resection; controls were followed for at least 4.5 years without recurrence. Specimens were re-reviewed by a single pathologist. Tumor FFPE slides were macrodissected and RNA extracted. CCP score, sex, age, T stage, Fuhrman Nuclear grade (FNG), tumor size, smoking status, lymphovascular invasion (LVI), and time to metastasis were available for analysis. Univariate and multivariate analyses were used to evaluate association with metastatic progression. Subsequently, the tumor transcriptome was interrogated for other informative biomarkers using next-generation sequencing (NGS). Funding was by Myriad Genetics. Results: Twenty-six cases and 38 controls were evaluated. Median time to metastasis was 1.68 years (IQR 1.06-3.69) for the case group. Median follow-up was 6.69 years for controls. Univariate analysis revealed that LVI (OR 4.64, p=0.005), FNG (OR 4.16, p=0.0099) and CCP score (OR 2.65, p=0.0091) were significantly associated with progression to metastasis. In multivariate analysis, age (p=0.026), tumor size (p=0.022) and CCP score (p=0.026) were statistically significant. A step-wise multivariate model including age, CCP, tumor size and LVI had an AUC of 0.84, which decreased to 0.78 if CCP score was excluded. CCP scores calculated by qPCR and NGS were correlated (rho = 0.91). However, no other genes showed a significant association with metastasis or TNM stage (after correcting for multiple testing) in univariate analysis or after adjusting for CCP score. Conclusions: The cell cycle progression score predicts metastatic progression after resection of ccRCC and appears to add significant prognostic information to standard clinical and pathological variables.