Accordingly, Abruzzese and colleagues found high pIR-positive staining during the transition from normal colorectal epithelium to colon adenomas and adenocarcinomas, with strong pIR expression in adenomas and low-grade adenocarcinomas, suggesting that activation of the insulin/IR axis is an early event in colorectal carcinogenesis (Figure 1B) (17). This evidence concerns the gene PIR and colon adenoma.