Multistep mouse mammary tumorigenesis through pre-neoplasia to neoplasia and acquisition of metastatic potential

Abstract

Human breast tissue can give rise to hyperplasias, atypical hyperplasias, and in situ carcinomas originating in a terminal duct-lobular unit (TDLU). These entities are associated with increased risk of subsequent development of invasive carcinoma. Human breast carcinomas arise via intermediate steps known as precursor or premalignant lesions. However, it is difficult to perform stepwise observation of the progression of human breast cancer. Mouse mammary tissue can give rise to several characteristic types of premalignant hyperplasia and tumor, originating in a duct or acinus, that progress to carcinoma. Three specific types of mouse mammary lesion with premalignant potential have been identified: hyperplastic alveolar nodule (HAN), plaque (PLQ), and ductal hyperplasia (DH). These lesions partially resemble human precursor lesions, and clarification of similarities and differences between the human and mouse lesions could improve our understanding of human breast carcinogenesis. Some invasive breast carcinomas acquire metastatic potential and may cause the death of the patient. Because the most malignant aspect of neoplasia is metastasis, recognition of metastatic phenotypes is particularly important. Mouse mammary carcinomas rarely metastasize, but there exist mouse models of metastasis of mammary carcinoma. In the present review article, we describe morphological, biological, and molecular aspects of premalignant lesions of mice, and we discuss their metastatic phenotypes.