Extended Data Fig. 2: Histopathology of Zeb2^IEC-Tg/+ mice.

a, Representative H&E stained colon section from wild-type control mouse showing normal proximal colon (representative for n=10 mice). Left panel, magnification of boxed area. b, Representative H&E stained sections of Zeb2^IEC-Tg/+ mouse (representative for n=7 mice) demonstrating multicentric invasive adenocarcinoma in a background of atypical mucosal hyperplasia with multifocal intraepithelial neoplasia and intramucosal carcinoma. Also sparse inflammatory cell infiltrates, predominantly lymphocytes and plasma cells, can be observed in the lamina propria and submucosa. Left panel, higher magnification showing severe atypical hyperplasia/intramucosal carcinoma characterized by tumultuous proliferation of irregular glandular units (upper), and of the invading adenocarcinomatous component characterized by irregular glandular profiles with abundant mucus collection, transmural infiltration of the intestinal wall and spread along the mesenteric ligament (lower). c, PAS staining of section of distal colon and rectum of Zeb2^IEC-Tg/+ mouse (representative for n=7 mice). Abundant collection of PAS-positive mucus is evident in the irregular neoplastic glandular units transmurally invading the intestinal wall and infiltrating along the mesenteric ligament. d, Macroscopic view on proximal colon tissue dissected in 44-week old WT and Zeb2^IEC-Tg/+ mice. e, Macroscopic dissected proximal colon in 31-week old Zeb2^IEC-Tg/+ mouse displaying transmural cancerous outgrowth.