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

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 -