Progression of premalignant MCF10AT generates heterogeneous malignant variants with characteristic histologic types and immunohistochemical markers

The MCF10AT premalignant human breast epithelial cells form benign ductal s tructures in immunodeficient mice which sporadically progress to carcinoma in situ and invasive cancers of different histologic types. MCF10CA1 cell l ines are malignant variants derived by serially passing small pieces of tum ors in athymic mice before establishing cells in culture. As these MCF10CA1 variants gave rise to heterogeneous tumors, some cell lines were cloned. I noculated into immunodeficient mice, these variants produce squamous carcin omas with an undifferentiated component or adenocarcinomas also with an und ifferentiated component. Immunohistochemistry utilized antibodies against D F3, c-erbB-2, cyclin D1, m keratin, p keratin, p53, B72.3 and estrogen rece ptor. We detected characteristic patterns for squamous carcinomas, for aden ocarcinomas, and for each undifferentiated component, that is the undiffere ntiated components of the squamous and glandular carcinomas were distinct. Only adenocarcinomas were focally ER positive. One uncloned variant that pr oduced cancers with a glandular component, MCF10CA1h, was cloned and cells were injected into mice. This clone produced only undifferentiated carcinom as that, compared to tumors formed by the parental uncloned variant, had lo st ER, DF3 and c-erbB-2 expression, but more strongly expressed p53. Our da ta demonstrate the potential of the premalignant MCF10AT model to generate heterogeneity, including both estrogen receptor-positive as well as estroge n receptor-negative tumors, during progression.