IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer

Abstract

Background: The present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3) in patients with pancreatic cancer. The function of IGFBP3 is controversial, because both inhibition and facilitation of the action of IGF as well as IGF-independent effects have been reported. In this study, IGF1R and IGFBP3 expression was examined, and their potential roles as prognostic markers in patients with pancreatic cancer were evaluated.

Methods: Clinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed.

Results: Expression of IGF1R and IGFBP3 was observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression was significantly associated with histological grade (p = 0.037). IGFBP3 expression had a significant association with tumor location (p = 0.023), and a significant inverse association with venous invasion (p = 0.037). Tumors with IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive patients was significantly poorer than that for IGF1R negative patients (p = 0.0181). IGFBP3 protein expression did not correlate significantly with patient survival. The subset of patients with both positive IGF1R and negative IGFBP3 had worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001).

Conclusion: IGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R expression and low IGFBP3 expression represent useful prognostic markers for patients with curatively resected pancreatic cancer.

Figure 1

IGF1R and IGFBP3 expression in pancreatic cancer. A, Representative IGF1R staining quantified with scores of 0 to 3+ according to staining intensity. (Original magnification X 200). IGF1R was mainly expressed in the cytoplasm of pancreatic cancer cells. B, IGFBP3 was expressed in the cell membrane and the cytoplasm of pancreatic cancer cells.

Figure 2

Overall survival of patients based on IGF1R and IGFBP3 expression. The survival curve shows the Kaplan-Meier overall survival curves in relation to the IGF1R and IGFBP3 levels in patients with pancreatic cancer. A statistically significant difference in survival was observed between patients with IGF1R-positive and IGF1R-negative tumors (p = 0.018). The prognosis of patients with IGF1R-positive and IGFBP3-negative patients showed a significant correlation with overall survival (p < 0.001). IGFBP3 expression alone tended to be associated with overall survival (p = 0.079). The co-expression of IGF1R-negative and IGFBP3-positive PDAC was not associated with overall survival (p = 0.218).

Figure 3

Overall survival stratified by IGF1R and IGFBP3 expression in cancer cells in patients with clinical stage II tumors. Prognosis of IGF1R-positive cancer was significantly poorer (p = 0.008) than that of IGF1R-negative cancer in the stage II group. Analysis of prognosis of patients with IGF1R-positive and IGFBP3-negative tumors shows a significant correlation with overall survival (p = 0.0009) in patients with stage II tumors.