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

Journal article
Authors W. Boecker
Göran Stenman
T. Loening
Mattias K Andersson
A. Bankfalvi
S. von Holstein
S. Heegaard
A. Lange
T. Berg
V. Samoilova
K. Tiemann
I. Buchwalow
Published in Modern Pathology
Volume 26
Issue 8
Pages 1086-1100
ISSN 0893-3952
Publication year 2013
Published at Institute of Biomedicine, Department of Pathology
Sahlgrenska Cancer Center
Pages 1086-1100
Language en
Links dx.doi.org/10.1038/modpathol.2013.4...
Keywords keratin 5, keratin 14, p63, progenitor cells, salivary gland-like breast tumors, triple-, adenoid cystic carcinoma, copy number alterations, malignant, myoepithelioma, pleomorphic adenoma, electron-microscopy, intercalated, ducts, spindle-cell, gene fusion, stem-cells, adenomyoepithelioma
Subject categories Clinical Medicine

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 = 8), epithelial-myoepithelial tumors (n = 9), and adenoid cystic carcinomas (n = 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.

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