They demonstrated a uniform immune-histochemical expression of NOTCH1 and HES1 in well-differentiated rectal NENs—found to be, respectively, 100% and 64%—whereas only 34% and 10% of well-differentiated pancreatic NENs were positive for NOTCH1 and HES1 at immunohistochemistry, and all ileal NENs were negative to both, suggesting a possible different role of NOTCH1 in the pathogenesis of these cancers. This evidence concerns the gene NOTCH1 and cancer.