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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

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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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Acknowledgments

Part of this study was supported by grants from the Swedish Cancer Society and BioCARE—a National Strategic Research Program at the University of Gothenburg.

The abstract with a title: “A discrete population of p63+/K5/14+ cells implicated in the pathogenesis of salivary gland-like tumors of the breast” has been selected for presentation at the 2013 San Antonio Breast Cancer Symposium, December 10–14, 2013 in San Antonio, Texas.

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The authors declare no competing financial interests.

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Correspondence to Werner Boecker.

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The authors dedicate this work to Prof. Dr. Dr. mult. Ekkehard Grundman, the predecessor of W. Boecker on the chair of Pathology at the University of Münster.

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Boecker, W., Stenman, G., Loening, T. et al. Squamous/epidermoid differentiation in normal breast and salivary gland tissues and their corresponding tumors originate from p63/K5/14-positive progenitor cells. Virchows Arch 466, 21–36 (2015). https://doi.org/10.1007/s00428-014-1671-x

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