Preneoplastic and Precancerous Lesions in Rodents: Morphologic and Molecular Characteristics.

Abstract

Cancer evolves through a sequential process from normal cells in many tissues of humans and animals. The natural history of tumor development can be seen histologically and by biochemical and molecular changes. There are two common basic pathways for the formation of malignant epithelial tumors; through preneoplastic foci and benign tumors (carcinoma developing in an adenoma) in parenchymal tissue or progression from intraepithelial neoplasia (IN) (atypical hyperplasia, noninvasive carcinoma, carcinoma in situ), a lesion in flat or lining epithelium. In epithelial-lining tissues of humans and rodents (e.g. cervix, mammary gland, prostate, skin), these lesions have been described as IN. In solid epithelial organs (liver, kidney, endocrine tissues) focal hyperplasia leads to adenomas. Adenomas develop foci of carcinoma, a process that is more common in rodents than in humans. These precancerous lesions in many rodent tissues often have multiple biochemical and molecular lesions which can be similar or different from those found in malignant tumors. The rodent molecular lesions include mutations in oncogenes (K-ras, H-ras) and tumor suppressor genes (p53, β-catenin, apc) or loss of heterozygosity (LOH) in tumor suppressor genes of mutant mouse models. This manuscript will review specific sequential morphologic and molecular lesions in the histopathogenesis of cancer in several rodent tissues. The significance of molecular lesions for diagnosis of rodent lesions will be discussed.