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. Author manuscript; available in PMC: 2015 Jul 11.
Published in final edited form as: Nature. 2014 Jul 2;513(7516):110–114. doi: 10.1038/nature13441

Figure 4. Mutant IDH cooperates with KrasG12D to drive liver progenitor cell expansion and multi-step IHCC pathogenesis.

Figure 4

a. Kaplan-Meier analysis showing time until signs of illness necessitated euthanasia. All animals euthanized had liver tumours.

b. Upper left: Representative Alb-Cre;LSL-R172K;KrasG12D tumor, and peritoneal and spleen metastases (insets). Upper right: H&E staining showing IHCC histology. Lower panels: The tumour is Hep Par1- and CK19+ while adjacent hepatocytes stain Hep Par1+ and CK19-.

c.The livers of Alb-Cre;LSL-R172K;KrasG12D animals exhibit oval cell expansion and increasing grades of BilIN, which stain Sox9+. CK19 levels increase with higher grade lesions. IF analysis reveals focal accumulation Sox9+ oval cells in Alb-Cre:LSL-R172K livers and pronounced oval cell expansion in Alb-Cre;LSL-R172K; KrasG12D livers.

d. Model for mutant IDH in cholangiocarcinoma pathogenesis. Scale bars, 1cm (b, upper left), 50µm (b-c).