Finally, while the normal Ki-67 proliferation index is 5% in nonneoplastic epithelium, with Ki-67 staining seen mostly in the base of crypts, the Ki-67 index is 37% in low grade adenomas, 32% in high grade adenomas, and 41% in invasive carcinomas; this early increase in cell proliferation mirrors the increased expression of beta-catenin and cyclin-D1. Here, CCND1 is linked to invasive carcinoma.