Abstract

BackgroundThe 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.MethodsClinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed.ResultsExpression 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).ConclusionIGF1R 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.

Highlights

  • The present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and insulinlike growth factor (IGF) binding protein-3 (IGFBP3) in patients with pancreatic cancer

  • IGF1R signaling might be associated with tumor aggressiveness, and IGF binding protein-3 (IGFBP3) might show antiproliferative effects in pancreatic cancer

  • Previous studies have shown an association between progression of Pancreatic ductal adenocarcinoma (PDAC) and overexpression of several growth factors including insulinlike growth factor (IGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) [6,7,8]

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Summary

Introduction

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 management and treatment of patients with pancreatic cancer have improved over the last few decades, the overall 5-year survival rate remains less than 5% [2]. Graduate School of Medicine, 1-4-3 Asahi-machi, Osaka, Abeno-ku 545-8585, Japan operation, with overall 5-year survival rates ranging from 10% to 25% [3,4]. The high mortality rate associated with pancreatic cancer is known to be due to extensive invasion into surrounding tissues and metastasis to distant organs at the time of diagnosis (or even after a curative operation); the molecular mechanisms of the highly aggressive nature of PDAC remains unclear [5].

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