REG4 and neoplasm: Intestinal neuro-endocrine tumors of both low and high grade also show REG4 positivity, frequently with a peculiar anatomical distribution with the strongest expression in a single layer of cells in the periphery of the tumor that are in intimate contact with the surrounding stroma [6] Given this, it was somewhat intriguing that synaptophysin- and chromogranin-positive CRC tumors in this study remained negative for REG4.