Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma.

Abstract

The development of scoring systems that combine pathological and clinical characteristics of clear cell renal cell carcinoma (CC-RCC) have improved outcome prediction in patients with CC-RCC. However, these scoring systems represent surrogate markers of the underlying molecular mechanisms of tumor aggressiveness and provide no tangible targets for potential therapy. As such, there is a need to identify molecular prognostic markers and potential targets of therapy for CC-RCC. Recent studies suggest that the insulin-like growth factor-I receptor (IGF-IR) may have prognostic value for patients with CC-RCC. Using a large, clinic based cohort of 280 patients who had CC-RCC treated with radical nephrectomy, we tested the hypothesis that the immunohistochemical detection of IGF-IR expression in CC-RCC is associated with poorer cancer specific survival. Kaplan-Meier analysis suggested that patients with IGF-IR positive CC-RCC experienced significantly decreased cancer specific survival than those with IGF-IR negative CC-RCC. The difference in survival was apparent within 2 years after surgery and it remained throughout followup. Based on a Cox proportional hazard model adjusting for age and sex patients with tumors that showed IGF-IR expression had a 70% increased risk of death due to CC-RCC than patients who had tumors without IGF-IR expression (HR = 1.7, 95% CI 1.2 to 2.6). The risk of CC-RCC death increased in individuals with greater than 50% IGF-IR expression (HR = 1.9, 95% CI 1.2 to 3.0). Adjustment for the Mayo Clinic Stage, Size, Grade and Necrosis Score attenuated the risk estimates but did not completely explain the association. Evidence from this investigation is consistent with laboratory data suggesting that IGF-IR expression is associated with CC-RCC survival and could potentially represent a molecular avenue for therapeutic intervention.