Expression of IGF-1R in Colorectal Polyps and its Role in Colorectal Carcinogenesis

Abstract

Insulin-like Growth Factor Receptor 1 (IGF-1R) may play a role in the neoplastic progression of colorectal cancer because it is related to both cellular proliferation and differentiation. The aim of this study was to further elucidate the role of IGF-1R in colorectal carcinogenesis by evaluating IGF-1R expression in different types of precancerous colorectal polyps and comparing its expression to normal mucosa and colorectal carcinoma. A total of 47 colorectal polyps and their respective adjacent normal mucosa were collected from 32 patients. In addition, 20 colorectal adenocarcinoma tissues were obtained from patients undergoing colorectal resection, and 12 normal non-malignant colorectal mucosal tissues collected from outpatients served as the control group. The pit patterns of polyps were classified by the Kudo classification scheme through magnifying chromoendoscopy. Immunohistochemistry and quantitative real-time RT-PCR were utilized for expression analysis of IGF-1R in colorectal mucosa, polyps, and adenocarcinoma tissue. The results of immunohistochemistry showed no significant differences in IGF-1R expression in inflammatory polyps compared with their surrounding normal mucosa by the Mann-Whitney U test (p=0.251); however, tubular adenoma and villous adenoma tissues exhibited significantly higher levels of IGF-1R expression (p=0.000). The results of real-time RT-PCR showed that IGF-1R was transcribed at a high level in colorectal adenomatous polyps and adenocarcinoma compared with their respective paired normal mucosa. Spearman's rank correlation two-variable analysis was used to demonstrate a significant correlation between the expression of IGF-1R and neoplastic progression from normal mucosa to adenomatous polyps and finally to colorectal cancer (r=0.574, p=0.000). This study suggests that the expression of IGF-1R correlates with the degree of carcinogenesis. In addition, these results demonstrated that there is a significant correlation between the level of IGF-1R expression and pit patterns of polyps (r=0.432, p=0.002). Thus, IGF-1R might be a factor in the morphological change of colorectal mucosal crypts, and it may play an important role in the growth and malignant transformation of precancerous polyps. These results suggest that IGF-1R can be considered a biomarker for the stage and risk of carcinogenesis during neoplastic initiation and progression along the colorectal normal mucosa-polyp-cancer sequence. Inhibitors of IGF-1R are not only a promising targeted anticancer strategy, but also a possible option for the chemoprevention of colorectal cancer.