Abstract P6-01-07: New Concept of the Histogenesis of Salivary Gland-Like Tumors of the Breast as K5/14-Positive Progenitor Lesions
Authors: W Boecker, A Bankfalvi, C Hallas, I Buchwalow, H Herbst, T. Loening
Journal: Cancer Research (2010)

Abstract Background: As an exocrine gland, the breast can manifest tumors with similar morphological features as the salivary gland. Defining the cellular identity of such tumours is one of the keys to a better understanding how these tumors evolve and grow. Material and Methods: We analyzed corresponding counterpart tumors such as pleomorphic adenoma, basal-cell adenoma, adenoid cystic carcinoma, adenosquamous carcinoma, and adenomyoepithelial tumors. With basal keratins, K5 and K14, as a reference, we have used antibodies against glandular keratins 8/18, myoepithelial markers (SMA, SMMHC, CD10) and functional markers such as Ki67 to investigate their expression in breast and salivary gland tumors. We used modern triple immunofluorescence labeling for simultaneously detecting these proteins in tumour cells with the obj ective to define different cell lineages and their differentiation status. The data were corroborated by real time PCR analysis of cRNAs for these proteins. Drawing parallels between tumors of the breast and salivary gland must help to unravel the nature of these lesions in these two organs. Results: All salivary gland tumors were found to contain progenitor cells with expression of basal keratins 5/14. They also showed an orderly sequential expression of basal keratins 5/14 and lineage specific proteins K8/18 for the glandular differentiation, myoepithelial markers for the myoepithelial differentiation, and K10 and vimentin for heterologeous squamous and mesenchymal differentiation, respectively, indicating the evolution of lineage specific cells from K5/14+ precursor cells. Normal breast and salivary gland epithelium showed striking similarities in their cellular composition, as both glands contain K5/14-positive progenitor cells which differentiate to glandular (K8/18+) or myoepithelial (SMA+;SMMHC+, CD10+) cells via intermediary cells, with a sequential expression of basal and lineage specific proteins. However, there are striking differences in the proliferative activity of different subtypes of cells — for instance, of precursor cells and differentiating glandular cells in both organs, which might be the source of differences in incidence of these tumors in both glands. Discussion: In this study we show that: (i) with few exceptions, salivary gland-like tumours represent K5/14- positive tumors with a glandular and/or myoepithelial differentiation and/or with a heterologeous (for example squamous) differentiation; (ii) the corresponding counterpart tumors both of breast and salivary gland are identical. As the constituent cells of all these tumors mimic the cellular composition and differentiation capabilities of progenitor cells both of breast and salivary gland epithelium, we believe that these tumors may originate from immature, probably pluripotent K5/14+ progenitor cells. Differences in proliferative activity of the various subtypes of cells in both organs might be an explanation for their rather different incidences. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-07.