Metaplastic breast carcinoma: tumour histogenesis or dedifferentiation?

Global gene expression profiling studies have classified breast cancer into molecular classes, some of which show similarity to normal mammary cells (ie luminal and basal subtypes) with a subsequent histogenetic implication that reinforced the perception that the phenotype of breast cancer reflects the cell of origin. However, it remains to be determined whether phenotypic changes are the result of malignant transformation of particular cancer stem cells (histogenesis) or specific genetic hits occurring at various stages of carcinogenesis (dedifferentiation). We sought to test the hypothesis that dedifferentiation may be the more likely explanation using in vivo clinical data. Our findings support the hypothesis that at least some metaplastic carcinomas are derived from phenotypic transition from conventional mammary adenocarcinoma either at the in-situ, primary invasive stage or at a distant metastatic site. This observation argues against the cell of origin theory (histogenesis) for breast carcinogenesis and favours the concept of tumour dedifferentiation at later stages.