Insulin-like growth factor-1 receptor expression and disease recurrence and survival in patients with resected pancreatic ductal adenocarcinoma.

Background:Insulin-like growth factor-1 receptor (IGF1R) signaling is important in pancreatic ductal adenocarcinoma (PDAC) biology, but little is known regarding IGF1R expression and patient characteristics and outcomes. Methods:In 365 patients with resected PDAC we evaluated IGF1R protein expression using immunohistochemistry on whole-slide sections and IGF1R genomic status using next-generation sequencing. Associations of IGF1R expression, measured by H-scores incorporating staining intensity and proportion of positive tumor cells, with disease-free survival (DFS) and overall survival (OS) were evaluated in 317 and 321 patients, respectively, using Cox regression adjusting for known prognostic factors. Results:Higher IGF1R expression in tumor cells was associated with worse DFS comparing highest vs. lowest expression tertiles (median DFS, 10.8 vs. 16.1 months; adjusted hazard ratio [HR], 1.73; 95% CI, 1.24-2.44; Ptrend=0.002) and worse OS (median OS, 17.4 vs. 25.8 months; HR, 1.39; 95% CI, 1.00-1.92; Ptrend=0.046). The association between high IGF1R expression and reduced DFS was identified primarily among patients with a preoperative body mass index ≥25 kg/m2 (HR, 4.27; 95% CI, 2.03-8.96, comparing extreme tertiles; Pinteraction=0.032). KRAS-mutant tumors had greater IGF1R expression, and IGF1R expression in tumor epithelium was inversely correlated with that in stromal cells. Mutations in IGF1R were infrequent, and no overt loss of function alterations were identified. Higher IGF1R expression was modestly associated with higher gene copy number (Pearson correlation coefficient=0.26, P<0.001). Conclusions:Higher IGF1R protein expression was associated with worse patient outcomes in resected PDAC. Impact:IGF1 expression in PDAC represents a potential biomarker to guide patient selection for more aggressive, multi-drug regimens in the adjuvant setting.