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

Purpose: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.