APC and neoplasm: However, canonical Wnt signaling and β-catenin alone appear not to be the sole driving force behind tumor budding, as nuclear β-catenin at the invasive tumor front did not necessarily predict budding (32, 33) and although up to 90% of all colorectal cancers have dysregulation of Wnt signaling and 60% harbor APC mutations (34), high-grade budding is only seen in a proportion of these (around 40%), depending on case mix and evaluation methods (9, 14, 35–37).