Expression of Insulin-like Growth Factor-I-Receptor in Colorectal Adenomas and Carcinomas

ABSTRACT

The activation of the insulin-like growth factor-I-receptor system (IGF-IR) has recently emerged as critical events in transformation and tumorigenicity of several human tumors. In this study we investigated the expression of IGF-IR in 33 colorectal adenomas, 88 primary colorectal carcinomas, and 30 normal colonic mucosa adjacent to the carcinoma. Immunohistochemical staining (IHC) for IGF-IR was performed on paraffin embedded sections using an anti-IGF-IR rabbit polyclonal antibody. IHC stains for IGF-IR were scored using a semiquantitative scoring system. The relationship of IGF-IR staining to clinicopathologic variables and proliferating cell nuclear antigen (PCNA) staining was also analysed. The mean IHC scores for IGF-IR of normal glands, adenoma, intramucosal carcinoma, node-negative carcinoma, and node-positive carcinoma were 0.41 0.96, 0.76 1.23, 2.0 1.48, 2.83 2.0 and 5.93 1.58, respectively. These scores for each category were statistically significant except between normal glands and adenoma and between intramucosal carcinoma and node-negative carcinomas. The mean PCNA indexes of normal glands, adenoma, intramucosal carcinoma, node-negative carcinoma, and node-positive carcinoma were 2.48 2.60, 6.94 11.03, 27.21 11.42, 43.36 9.9 and 57.60 10.01, respectively. The PCNA index for each category was statistically significant except between normal and adenoma. IGF-IR scores and PCNA indexes were higher with tumor progression and also correlated each other (sr=0.65, p=0.0001). Higher IGF-IR scores and PCNA indexes were seen in tumors with advanced stage, infiltrative growth pattern, poor differentiation, nerve invasion, lymphovascular invasion, and moderate fibrosis. Our results suggest that IGF-IR plays an important role in tumorigenicity and tumor progression.