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. 2021 Sep;191(9):1651–1667. doi: 10.1016/j.ajpath.2021.05.017

Figure 1.

Figure 1

Overview of Notch1 intracellular domain (Nicd)–induced cholangiocarcinogenesis. A–D: Hematoxylin and eosin (HE) staining of early [20 weeks post injection (w.p.i.), A and C] and late (32 w.p.i., B and D) cholangiocellular lesions developed in the mouse liver after hydrodynamic gene delivery of the activated/cleaved Nicd plasmid. Representative cystadenoma lesion (arrows) consisting of multiple cysts (A). Higher magnification image showing the cystic formations lined by a flat or cuboidal epithelium composed of cytologically benign cells (C). At later time points, invasive cystadenocarcinoma (CAK) and intrahepatic cholangiocarcinomas (iCCA), often co-expressing, were detected on the liver surface of Nicd-overexpressing mice (B). At high magnification, the iCCA appears to be composed of highly malignant cells and frequent mitoses (D). E–H: Both early and late lesions display positive immunoreactivity for the biliary marker cytokeratin 19 (CK19) (E) and the injected pT3EF1α-NICD (Myc-tagged) plasmid (H). Scale bars = 200 μm (A and B); 50 μm (C–H). Original magnification: ×40 (A and B); ×400 (C–H).