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Squamous/epidermoid differentiation in normal breast and salivary gland tissues and their corresponding tumors originate from p63/K5/14-positive progenitor cells

Journal article
Authors W. Boecker
Göran Stenman
T. Loening
Mattias K Andersson
T. Berg
A. Lange
A. Bankfalvi
V. Samoilova
K. Tiemann
I. Buchwalow
Published in Virchows Archiv
Volume 466
Issue 1
Pages 21-36
ISSN 0945-6317
Publication year 2015
Published at Sahlgrenska Cancer Center
Pages 21-36
Language en
Links dx.doi.org/10.1007/s00428-014-1671-...
Keywords Tumors of breast and/or salivary glands with squamous/epidermoid differentiation, Squamous cell, GENE-EXPRESSION PATTERNS, P53 HOMOLOG P63, MYOEPITHELIAL CELLS, SQUAMOUS, METAPLASIA, EPITHELIAL-CELLS, SMOOTH-MUSCLE, MUCOEPIDERMOID CARCINOMA, ADENOSQUAMOUS CARCINOMA, STROMAL MYOFIBROBLASTS, MONOCLONAL-ANTIBODY, Pathology, SCHINI MP, 1995, VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY, V427, P243, CARTHY KP, 1994, MOLECULAR BIOLOGY REPORTS, V19, P69
Subject categories Clinical Medicine

Abstract

A small group of tumors of breast and salivary glands contains squamous/epidermoid elements as a constitutive feature (e.g., squamous carcinoma, syringomatous tumors, and mucoepidermoid carcinoma). Other tumors (e.g., pleomorphic adenoma, adenomyoepithelial tumors, and adenoid cystic carcinoma) may show occasionally squamous differentiation. Furthermore, squamous metaplasia may be observed in non-neoplastic breast and salivary tissues. However, the histogenesis of these squamous differentiations is far from being understood. Based on our earlier in situ triple immunofluorescence and quantitative reverse transcription (RT)-PCR experiments for basal keratins K5/14 and p63 as well as for glandular keratins (K7/K8/18), squamous keratins (K10 and K13), and myoepithelial lineage markers (smooth muscle actin, SMA), we here traced the squamous/epidermoid differentiation lineage of 60 tumors of the breast and/or salivary glands, cultured tumor cells of 2 tumors, and of 7 squamous metaplasias of non-neoplastic breast and salivary tissues. Our results indicate that both the neoplastic lesions as well as the non-neoplastic squamous metaplasia contain p63/K5/14+ cells that differentiate toward K10/13+ squamous cells. Thus, cells with squamous/epidermoid differentiation undergo a transition from its original p63/K5/14+ precursor state to K10/13+ squamous lineage state, which can be pictured by triple-immunofluorescence experiments. Given the immunophenotypic similarity of p63/K5/14+ tumor cells to their physiological p63/K5/14+ counterparts in normal breast and salivary duct epithelium, we suggest that these cells provide an important histogenetic key to understanding the pathogenesis of squamous differentiation both in normal breast/salivary gland tissues and their corresponding tumors.

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