• mutants develop diffuse liver dysplasia by 3 months of age

• 22% of mutants develop hepatocellular carcinomas by 6 months of age and by 9 months of age, 100% of mutants show hepatocellular carcinomas, indicating that tumors are more severe and arise faster than in single transgenic mice

• tumors are predominantly moderately well differentiated with trabecular, solid and trabecular/pseudoglandular pattern

• liver tumor progression begins with preneoplastic foci adjacent to portal tracts and pericentral large cell dysplasia at 2 months of age, followed by an abrupt increase in the number of neoplastic nodules or adenomas from 4-6 months onward, with 100% incidence by 10 months of age, and finally some adenomas show evidence of malignant transformation into trabecular hepatocellular carcinoma (J:65354)

• 100% incidence of adenomas by 10-12 months of age

• mice show features of malignant transformation in some of the adenomas by 10 months of age (J:65354)

• 60% of mutants develop hepatocellular carcinoma by 12 months of age (J:101128)

• tumors are predominantly well-differentiated (J:101128)

• livers show an increase in cell proliferation; at one month of age, the proliferation index is increased about 1.4-fold compared to wild-type, then proliferation decreases at 2 months of age so it is 2-fold lower than at 1 months of age but it is 6-fold higher than in wild-type livers at this time

• macrovesicular hepatic steatosis is first seen in livers at 6-8 months of age and by 10-12 months of age, 60% of mutants develop prominent fatty change

• livers show an increase in cell proliferation; at one month of age, the proliferation index is increased about 1.4-fold compared to wild-type, then proliferation decreases at 2 months of age so it is 2-fold lower than at 1 months of age but it is 6-fold higher than in wild-type livers at this time