Although rare events, i.e. the possible occurrence of tiny populations of KIT negative PDE3A-ir cells or KIT-ir PDE3A negative cells, cannot be totally ruled out by these experiments, the presence of PDE3A-ir selectively in the KIT-ir ICC in the 3 genotypes studied and the ability of PDE3A-ir to detect, to the same extend as KIT-ir, the predicted ICC hyperplasia in the reference model for KIT-ir ICC hyperplasia, KitK641E mice, and in Spry4 KO colon comfort our view [19] that PDE3A-ir represents globally a valuable marker for the Kit-ir ICC in the WT mouse gut and in ICC hyperplasia models. This evidence concerns the gene PDE3A and intrahepatic cholangiocarcinoma.