Earlier onset of premalignant and malignant hepatic lesions in DEN-treated <i>Rap1</i>^<i>-/-</i> females.

(A) Representative light microscopy images of α-fetoprotein (AFP) and hematoxylin-eosin (H&E) liver sections showing the different types of lesions induced by DEN. Focus of AFP-positive hepatocytes, focus of altered hepatocytes (FAH), hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) are shown from left to right. For a detailed histological description see Material and Methods. (B-C) Quantification of FAHs and AFP-positive foci (B) and HCAs (C) in Rap1+/+ and Rap1-/- livers of female mice at 40 weeks after DEN injection. (D) Quantification of total number of HCC in Rap1+/+ and Rap1-/- livers of female mice at 40, 45–55 and 60–65 weeks post-DEN. (E) Quantification of the number of HCC of different size in the mice described in (D). (F) Incidence of lung metastasis in Rap1+/+ and Rap1-/- female mice between 45 and 65 weeks post-DEN. A representative light microscopy image of hepatocyte antigen-stained lung sections is shown to the right. Values and error bars represent the mean and SE, respectively. N, number of mice. Statistical significance was determined by Student’s t test.