Metaplastic breast carcinoma: tumour histogenesis or dedifferentiation?

Abstract

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.

EMT in carcinoma progression and dissemination: Facts, unanswered questions, and clinical considerations

“…Metaplastic carcinomas are of interest because they include malignant cells that can produce cartilage or bone, which may imply dedifferentiation into cells with capacities allotted to the mesenchymal lineage. Indeed, the mesenchymal components probably arose, at least in some cases, from the carcinomatoid lesion [17]. Carcinosarcomas are rare, high grade, highly disorganized, and invasive tumors in which both the stromal and epithelial compartments are malignant.…”

Primary chondrosarcoma of the breast: a case presentation and review of the literature

“…Surgery remains the choice of treatment for most sarcomatoid tumors [6]. Multimodality treatment may decrease local and systemic recurrence rates of somatic sarcomas, but results are inconclusive in patients with breast sarcomas [7,8]. The role of chemotherapy and radiotherapy is not yet established because of the limited number of cases reported so far.…”

Tumour Heterogeneity of Breast Cancer: From Morphology to Personalised Medicine

“…In support of this, some authors have demonstrated that basal-like BC may arise from luminal progenitor cells [14]. Metaplastic trans-differentiation has been demonstrated, not only in the in-situ and invasive lesions but also at distant metastatic sites [12.] The phenomenon of epithelial-mesenchymal transition is well-documented in BC where malignant epithelial cells lose their junctional structures, express mesenchymal proteins, and remodel their extracellular matrix (ECM).…”

“…Mammary glandular cells show a high degree of phenotypic plasticity, which can be appreciated in both benign and malignant conditions [11,12,13]. These phenotypic alterations represent the expression of genotypic and molecular properties not present in normal mammary glandular cells, and in benign as well as some malignant conditions they are likely to be the result of de-repression of the normally coded molecular mechanisms responsible for the epithelial phenotype rather than histogenesis [11,12,13].…”

“…These phenotypic alterations represent the expression of genotypic and molecular properties not present in normal mammary glandular cells, and in benign as well as some malignant conditions they are likely to be the result of de-repression of the normally coded molecular mechanisms responsible for the epithelial phenotype rather than histogenesis [11,12,13]. In support of this, some authors have demonstrated that basal-like BC may arise from luminal progenitor cells [14].…”