Figure 4.

SSP development in Sav1-deficient mouse colons and the prevalence of Hippo pathway dysregulation in human SSPs. (A) Distal colon of 13-mo-old wild-type control and Sav1-deficient littermates. Note the presence of two polyps in the Sav1-deficient colon (black arrows). (B) H&E staining of the colonic sections from 13-mo-old wild-type control (left) and Sav1-deficient (right) littermates. The top and bottom panels show the corresponding low- and high-magnification images, respectively. Note the presence of serrated polyps with “saw-tooth” crypt epithelium (asterisk in panel i), adenomatous transformation (arrow in panel ii), and invasion of the muscularis mucosa (arrow in panel iii) in Sav1-deficient colons. (C) Ki67 staining. Note that Ki67-positive proliferating cells were restricted to the crypt base in control colons. In Sav1-deficient colons, scattered Ki67-positive cells were detected throughout the crypt epithelia. (D,E) YAP and β-catenin staining. Note the accumulation of nuclear YAP but not nuclear β-catenin in Sav1-deficient colonic polyps (arrows). (F–J) Analysis of human SSPs. (F) Summary of YAP and β-catenin staining in human SSPs. (G) Histopathology of a right-sided SSP obtained by endoscopic excision. H&E stain, 10× magnification. Note the characteristic polypoid epithelium. (H) Up-regulation of YAP in the polypoid epithelium of an SSP compared with adjacent normal colonic epithelium. At the bottom right half of the panel, one gland was partially involved by SSP and demonstrated YAP up-regulation (white arrowhead), while the nonneoplastic half of the gland had minimal expression (black arrowhead). (I) High-power magnification of SSP epithelium with nuclear YAP labeling. Magnification, 40×. (J) Absence of nuclear β-catenin, with retained membranous localization of the protein, in the serial section of the SSP shown in D. Magnification, 40×. Bars, 100 μm.