K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation

Abstract

Salivary gland-like tumors of the breast show a great variety of architectural patterns and cellular differentiations such as glandular, myoepithelial, squamous, and even mesenchymal phenotypes. However, currently little is known about the evolution and cellular differentiation of these tumors. For that reason, we performed an in situ triple immunofluorescence lineage/differentiation tracing (isTILT) and qRT-PCR study of basal (K5/K14), glandular (K7/K8/18), and epidermal-specific squamous (K10) keratins, p63, and smooth muscle actin (SMA; myoepithelial marker) with the aim to construct and trace different cell lineages and define their cellular hierarchy in tumors with myoepithelial differentiation. isTILT analysis of a series of 28 breast, salivary, and lacrimal gland tumors, including pleomorphic adenomas (n ¼ 8), epithelial-myoepithelial tumors (n ¼ 9), and adenoid cystic carcinomas (n ¼ 11) revealed that all tumor types contained K5/K14-positive progenitor cells in varying frequencies from a few percent up to 15%. These K5/K14-positive tumor cells were found to differentiate to glandular-(K8/18-positive) and myoepithelial-lineage (SMA-positive)-specific cells and were also shown to generate various heterologeous cell differentiations such as squamous and mesenchymal progenies. p63 was co-expressed with K5/K14 in basal-like progenitor cells, myoepithelial, and squamous cells but not in glandular cells. Our results show that the corresponding counterpart tumors of breast and salivary/lacrimal glands have identical cellular compositions. Taken together, our isTILT and RNA-expression data indicate that look-alike tumors of the breast represent a special subgroup of basal-type tumors with benign or usually low malignant potential.

The unique luminal staining pattern of cytokeratin 5/6 in adenoid cystic carcinoma of the breast may aid in differentiating it from its mimickers

“…With regard to the origin of salivary gland-like breast tumors, including AdCC and adenomyoepithelioma, Boecker et al speculated that CK5/CK14-positive progenitor cells have a potential to differentiate to glandular and myoepithelial lineages and also to generate heterogeneous cell differentiation such as squamous and mesenchymal progenies [20]. It would be interesting to know molecular mechanisms driving reverse expression of CK5/6 in AdCC and both CK5/6 and CK14 in adenomyoepithelioma, since this may reflect differences in tumorigenesis between these closely related mammary neoplasms.…”

Phenotypic plasticity in normal breast derived epithelial cells

“…Boecker and colleagues recently published a study of salivary gland tumors of the breast and histologically similar tumors of the salivary and lacrimal glands [56]. They utilized triple immunofluorescence to trace the lineage of cells within these tumors.…”

Differentiation and histogenesis of syringomatous tumour of the nipple and low‐grade adenosquamous carcinoma: evidence for a common origin

“…FFPE sections (thickness, 4 μm) were pretreated and stained as described elsewhere . For immunostaining, we used primary antibodies raised against K5 (rabbit monoclonal; Medac Diagnostica, Hamburg, Germany); K5/6, K14 (basal markers), K7, K8, K8/18, K18 (glandular markers), and K10 (epidermal differentiation‐specific antibody used as a surrogate marker for squamous differentiation) (mouse monoclonals; Dako, Hamburg, Germany; Sigma, Hamburg, Germany; and Dianova, Hamburg, Germany); SMA (rabbit polyclonal; Abcam, Cambridge, MA, USA); vimentin (mouse monoclonal; Abcam and Dako); Ki67 (rabbit monoclonal; Thermo Fisher Scientific, Bonn, Germany); p63 (mouse monoclonal, clone 4A4; Dako); oestrogen receptors (rabbit monoclonal, clone SP1; Thermo Fisher Scientific); and HER2 (rabbit polyclonal; Medac Diagnostica).…”