TY - JOUR
T1 - K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation
AU - Boecker, Werner
AU - Stenman, Goeran
AU - Loening, Thomas
AU - Andersson, Mattias K
AU - Bankfalvi, Agnes
AU - von Holstein, Sarah
AU - Heegaard, Steffen
AU - Lange, Alina
AU - Berg, Tobias
AU - Samoilova, Vera
AU - Tiemann, Katharina
AU - Buchwalow, Igor
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Adenoma, Pleomorphic
KW - Breast Neoplasms
KW - Carcinoma, Adenoid Cystic
KW - Cell Differentiation
KW - Cell Lineage
KW - Diagnosis, Differential
KW - Female
KW - Fluorescent Antibody Technique
KW - Humans
KW - Myoepithelioma
KW - Real-Time Polymerase Chain Reaction
KW - Salivary Gland Neoplasms
KW - Stem Cells
KW - Tumor Markers, Biological
U2 - 10.1038/modpathol.2013.45
DO - 10.1038/modpathol.2013.45
M3 - Journal article
C2 - 23558567
SN - 0893-3952
VL - 26
SP - 1086
EP - 1100
JO - Modern Pathology
JF - Modern Pathology
IS - 8
ER -