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.