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- Boecker, W., et al.
(author)
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Differentiation and histogenesis of syringomatous tumour of the nipple and low-grade adenosquamous carcinoma: evidence for a common origin
- 2014
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In: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 65:1, s. 9-23
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Journal article (peer-reviewed)abstract
- Aims: Syringomatous tumour of the nipple and low-grade adenosquamous carcinoma (LGAdSC) of the breast are regarded as distinct entities. To clarify the nature of these two lesions, we compared the expression of different lineage/differentiation markers in 12 syringomatous tumours of the nipple, nine LGAdSCs, and normal breast epithelium. Methods and results: Using triple immunofluorescence labelling and quantitative RT-PCR for keratins, p63, and smooth muscle actin, we demonstrated that syringomatous tumour and LGAdSC contain p63+/K5/14+ tumour cells, K10+ squamous cells, and K8/18+ glandular cells, with intermediary cells being found in both lineages. Identical p63+/K5/14+ cells were also found in the normal breast duct epithelium. Conclusions: Our data provide evidence that syringomatous tumour of the nipple and LGAdSC are identical or nearly identical lesions. They contain p63+/K5/14+ cells as the key cells from which the K10+ squamous lineage and the K8/18+ glandular lineage arise. On the basis of our findings in normal breast tissue and associated benign lesions, we suggest that p63+/K5/14+ cells of the normal breast duct epithelium or early related cells might play a key role in the neoplastic transformation of both syringomatous tumour and LGAdSC. We propose that the differentiation patterns found in both lesions reflect the early ontogenetic stages of the normal breast epithelium.
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| 3. |
- Boecker, W., et al.
(author)
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K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation
- 2013
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In: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 26:8, s. 1086-1100
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Journal article (peer-reviewed)abstract
- 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.
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- Boecker, W., et al.
(author)
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Multicolor immunofluorescence reveals that p63-and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast
- 2017
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In: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 470:5, s. 493-504
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Journal article (peer-reviewed)abstract
- We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.
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| 5. |
- Boecker, W., et al.
(author)
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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
- 2015
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In: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 466:1, s. 21-36
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Journal article (peer-reviewed)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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