Myoepithelial tumors of the breast: A stem cell lesion with myoepithelial and glandular differentiation

Aims: Myoepithelial tumors (MT) of the breast are rare and so far described to represent a dual proliferation of both epithelial and myoepithelial cells. The aim of our study was to present a detailed analysis of benign and malignant MT using immunohistochemical (IH) and cytogenetic methods. Methods: IH studies of 17 benign adenomyoepitheliomas (AM), I benign myoepithelioma and 6 myoepithelial carcinomas (MC) were performed using antibodies directed against glandular cytokeratin (CK)8/18/19 and basal-type CK5/6, Ki-67/MIB1 and a-smooth-muscle(sm)-actin. Microdissected MT were analysed for genetic al-terations by comparative genomic hybridisation. Results: Myoepithelial immunoreactivity was demonstrated by staining with a-sm-actin. CK8/18/19 was expressed by glandular cells and CK5/6 by progenitor (stem) cells. Furthermore, digital double immunofluorescence staining revealed simultaneous expression of CK5/6 and a-sm-actin as well as CK5/6 and CK8/18/19 in a number of cells. The average number of genetic aberrations in all MT was 2,75 (range 1-10) compared with 6.7 (range 0-20) in invasive epithelial breast cancer as previously shown in one of our studies. Common alterations of MT shared with invasive epithelial breast cancer included gains at 8q (4/24) and losses at 6q (3/24), 17p (4/24) and 16q (2/24). Conclusions: These results strengthen the hypothesis that MT originate from progenitor, CK5/6-expressing stem cells giving rise to both glandular (CK8,18,19) and myoepithelial (a-sm-actin) cells through intermediary cells. Therefore, we regard myoepithelial tu-mors as neoplastic stem cell lesions with bidirectional myoepithelial and glandular differentiation. In one pure myoepithelioma, the glandular lineage could not be demonstrated. Thus, pure epithelial and myoepithelial tumors might represent the two ends of a spectrum of neoplastic epithelial-myoepithelial cell proliferations.