External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma

BACKGROUND. High-quality external validation studies have recently been high-lighted to be of paramount importance for proper translation of prognostic markers into the clinical setting. To that end, the authors examined associations of the insulin-like growth factor-II mRNA binding protein, IMP3, with clinical and pathologic features of clear cell renal cell carcinoma (ccRCC) in an independent cohort of patients to validate recent work showing IMP3 as a prognostic marker for RCC progression and death. METHODS. The authors studied 716 consecutive tumor specimens from patients treated with surgery at the study institution for unilateral, sporadic, noncystic ccRCC between 1990 and 1999. Tissues were stained and scored for IMP3 expression and these expression levels were correlated with clinical and pathologic features as well as clinical outcomes including progression to distant metastases and death from RCC. RESULTS. It was observed that 213 ccRCC specimens (29.8%) expressed tumor cell IMP3. IMP3 expression was associated with advanced stage and grade of primary tumors as well as other adverse features including coagulative tumor necrosis and sarcomatoid differentiation. After multivariate adjustment for ccRCC prognostic features, positive IMP3 expression was still found to be associated with a 42% increase in the risk of death from RCC (hazards ratio [HR], 1.42; P = .024). Among the subset of patients with clinically localized disease, positive IMP3 expression was associated with a nearly 5-fold increased risk of distant metastases (HR, 4.71; P < .001). CONCLUSIONS. Using a large and independent cohort of ccRCC patients, the authors confirmed that tumor cell IMP3 expression represents an independent predictor of aggressive ccRCC tumor behavior.