Pathologic T1 clear cell renal cell carcinoma: insulin-like growth factor-I receptor expression and disease-specific survival.

Abstract

A proportion of patients diagnosed with pathologic T1 (pT1) clear cell renal cell carcinoma (CC-RCC) will experience disease progression and death after surgery, whereas the majority remain disease free. The authors conducted a case-cohort investigation to examine the association of insulin-like growth factor I receptor (IGF-IR) expression and disease-specific survival in patients who underwent surgery for pT1 CC-RCC. Eligible patients included those diagnosed with solitary, nonfamilial pT1 CC-RCC who underwent radical nephrectomy at the Mayo Clinic-Rochester between 1970 and 2000 (n = 886 patients). Among this group, 136 patients died of CC-RCC (cases). Archived tumor blocks were not available for 62 patients, leaving a final study group of 74 cases. Stratified, random sampling was used to select a cohort of at least 3 year-matched controls (no CC-RCC death) for each case (n = 263 patients). Detection of IGF-IR was performed using a commercially available monoclonal antibody. Cox proportional hazards models were fit to assess the association between IGF-IR expression and disease-specific survival. After adjustment for age, the risk of death from CC-RCC was greater for patients who had tumors that stained positive for IGF-IR compared with patients who had tumors that showed no IGF-IR expression (hazard ratio [HR], 1.5; 95% confidence interval, [95% CI], 0.9-2.4). In a stratified analysis, the risk was stronger among patients who had high-grade tumors (HR, 2.2; 95% CI, 1.1-4.3) compared with patients who had low-grade tumors (HR, 0.7; 95% CI, 0.3-1.5). Multivariate adjustment for tumor size and histologic tumor necrosis attenuated the association among all patients (HR, 1.3; 95% CI, 0.8-2.1) but strengthened the association among patients with high-grade tumors (HR, 2.7; 95% CI, 1.3-5.6). The current data suggest that IGF-IR expression is associated with poor survival in patients who are diagnosed with early-stage CC-RCC, especially among those with high-grade disease.