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Histopathology Jun 2018Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many... (Review)
Review
Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is based typically on the presence of an intact barrier between the malignant epithelial cells and stroma; namely, the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in-situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non-infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may also be absent around some malignant lesions such as some forms of papillary carcinoma, yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM-like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics.
Topics: Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Epithelial Cells; Female; Humans; Stromal Cells
PubMed: 29197112
DOI: 10.1111/his.13446 -
Journal of Cellular Biochemistry Jul 2017To improve the precision of molecular diagnosis and to develop and guide targeted therapies of breast cancer, it is essential to determine the mechanisms that underlie... (Review)
Review
To improve the precision of molecular diagnosis and to develop and guide targeted therapies of breast cancer, it is essential to determine the mechanisms that underlie the specific tumor phenotypes. To this end, the application of a snapshot of gene expression profile for breast cancer diagnosis and prognosis is fundamentally challenged since the tissue-based data are derived from heterogonous cell types and are not likely to reflect the dynamics of context-dependent tumor progression and drug sensitivity. The intricate network of epithelial differentiation program can be concertedly controlled by tumor suppressor maspin, a homologue of clade B serine protease inhibitors (serpin), through its multifaceted molecular interactions in multiple subcellular localizations. Unlike most other serpins that are expressed in multiple cell types, maspin is epithelial specific and has distinct roles in luminal and myoepithelial cells. Endogenously expressed maspin has been found in the nucleus and cytoplasm, and detected on the surface of cell membrane. It is also secreted free and as an exosomal cargo protein. Research in the field has led to the identification of the maspin targets and maspin-associated molecules, as well as the structural determinants of its suppressive functions. The current review discusses the possibility for maspin to serve as a cell type-specific and context-sensitive marker to improve the precision of breast cancer diagnosis and prognosis. These advancements further suggest a new window of opportunity for designing novel maspin-based chemotherapeutic agents with improved anti-cancer potency. J. Cell. Biochem. 118: 1639-1647, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Breast Neoplasms; Epithelial Cells; Humans; Mammary Glands, Human; Precision Medicine; Serpins
PubMed: 28262971
DOI: 10.1002/jcb.25969 -
Laboratory Investigation; a Journal of... Nov 2022Myoepithelial (ME) cells in exocrine glands exhibit both epithelial and mesenchymal features, contributing to fluid secretion through contraction. However, the...
Myoepithelial (ME) cells in exocrine glands exhibit both epithelial and mesenchymal features, contributing to fluid secretion through contraction. However, the regulation mechanism of behind this unique phenotype in salivary glands remains unclear. We established a flow cytometry-based purification method using cell surface molecules, epithelial cell adhesion molecule (EpCAM) and alpha 6 integrin (CD49f), to characterize ME cells. EpCAMCD49f cells showed relatively high expression of ME cell-marker genes, such as alpha-smooth muscle actin (α-SMA). For lineage tracing and strict isolation, tdTomatoEpCAMCD49f-ME cells were obtained from myosin heavy chain 11 (Myh11) -CreER/tdTomato mice. Transcriptome analysis revealed that expression of genes involved in the epithelial-mesenchymal transition, including Snai2, were upregulated in the ME cell-enriched subset. Snai2 suppression in stable ME cells decreased α-SMA and increased Krt14 expression, suggesting that ME cell features may be controlled by the epithelial-mesenchymal balance regulated by Snai2. In contrast, ME cells showed reduced ME properties and expressed the ductal markers Krt18/19 under sphere culture conditions. Notch signaling was activated under sphere culture conditions; excessive activation of Notch signaling accelerated Krt18/19 expression, but reduced α-SMA and Snai2 expression, suggesting that the behavior of Snai2-expressing ME cells may be controlled by Notch signaling.
Topics: Mice; Animals; Integrin alpha6; Epithelial Cell Adhesion Molecule; Actins; Myosin Heavy Chains; Epithelial Cells; Muscle, Smooth; Salivary Glands; Biomarkers
PubMed: 35810235
DOI: 10.1038/s41374-022-00814-7 -
Head and Neck Pathology Mar 2023Myoepithelial neoplasms of the salivary gland are benign or malignant neoplasms composed exclusively of neoplastic myoepithelial cells. These tumors, including the... (Review)
Review
BACKGROUND
Myoepithelial neoplasms of the salivary gland are benign or malignant neoplasms composed exclusively of neoplastic myoepithelial cells. These tumors, including the benign myoepithelioma and the malignant counterpart myoepithelial carcinoma, exhibit a wide range of cytomorphologic features and architectural patterns.
METHODS
Review.
RESULTS
Myoepithelial cells can be epithelial, plasmacytoid, clear cell, spindle cell, and/or oncocytic cell, arranging as trabeculae, solid sheets, nests, cords, and/or single cells. A stromal component is commonly but not universally present, Therefore, their differential diagnoses are quite broad, including salivary gland neoplasms especially those with a myoepithelial component, plasmacytoma, melanoma, and various mesenchymal tumors.
CONCLUSION
In this review, we summarize the characteristic histologic features, useful immunohistochemical panel, and common molecular alterations of myoepithelial tumors and their top differential diagnoses. A logical stepwise algorithmic approach and an immunohistochemical panel to include multiple myoepithelial markers are essential to establish the correct diagnosis.
Topics: Humans; Biomarkers, Tumor; Immunohistochemistry; Salivary Gland Neoplasms; Salivary Glands; Myoepithelioma; Carcinoma
PubMed: 36928733
DOI: 10.1007/s12105-022-01502-0 -
Investigative Ophthalmology & Visual... Mar 2022To investigate microenvironment changes of the lacrimal gland after obstruction of lacrimal gland ducts.
PURPOSE
To investigate microenvironment changes of the lacrimal gland after obstruction of lacrimal gland ducts.
METHODS
The ducts of rat exorbital lacrimal gland were ligated by sutures for different durations. After that, the sutures in some animals were released, and they were observed for 21 days to evaluate the recovery of the lacrimal gland. Slit lamp and tear secretion test was performed to evaluate ocular surface and lacrimal gland function. The lacrimal gland and cornea were harvested and processed for hematoxylin and eosin staining, oil red O staining, LipidTOX staining, Masson staining, quantitative real time polymerase chain reaction, and immunofluorescence staining.
RESULTS
After the lacrimal gland ducts were blocked, tear secretion and the weight of the lacrimal gland were reduced. Incidence of corneal neovascularization increased after seven days. Intraglandular ducts dilated and acini destroyed. Long-term ligation induced fibrosis and lipid accumulation of the lacrimal glands. Inflammatory cell infiltrated and inflammatory factors upregulated. Proliferative and apoptotic cells increased. Structure of myoepithelial cells and basement membrane was destroyed. The p63 expression increased whereas Pax6 expression decreased. After suture release, tear secretion and structure of acini could recover in less than seven days after ligation, with a decrease in inflammatory cell infiltration and fibrosis relief. Apoptotic cells and proliferative cells increased at five days thereafter. The structure of the myoepithelial cells and basement membrane could not recover three days after ligation, and the number of mesenchymal cells increased in ligation after five to 14 days.
CONCLUSIONS
Blockage of the lacrimal gland ducts results in dystrophy of lacrimal gland acini cells, inflammation, and lipid accumulation of the lacrimal gland microenvironment. Long-term duct blockage will cause irreversible lacrimal gland failure.
Topics: Animals; Cornea; Fibrosis; Inflammation; Lacrimal Apparatus; Lipids; Rats
PubMed: 35289845
DOI: 10.1167/iovs.63.3.14 -
Pathology International May 2021Breast tissue has a branching structure that contains double-layered cells, consisting primarily of luminal epithelial cells inside and myoepithelial cells outside....
Breast tissue has a branching structure that contains double-layered cells, consisting primarily of luminal epithelial cells inside and myoepithelial cells outside. Ductal carcinoma in situ (DCIS) still has myoepithelial cells surrounding the cancer cells. However, myoepithelial cells disappear in invasive ductal carcinoma. In this study, we detected expression of neural EGFL like (NELL) 2 and one of its receptors, roundabout guidance receptor (ROBO) 3, in myoepithelial and luminal epithelial cells (respectively) in normal breast tissue. NELL2 also was expressed in myoepithelial cells surrounding the non-cancerous intraductal proliferative lesions and DCIS. However, the expression level and proportion of NELL2-positive cells in DCIS were lower than those in normal and non-cancerous intraductal proliferative lesions. ROBO3 expression was decreased in invasive ductal carcinoma compared to that in normal and non-cancerous intraductal proliferative lesions. An evaluation of NELL2's function in breast cancer cell lines demonstrated that full-length NELL2 suppressed cell adhesion and migration in vitro. In contrast, the N-terminal domain of NELL2 increased cell adhesion in the early phase and migration in vitro in some breast cancer cells. These results suggested that full-length NELL2 protein, when expressed in myoepithelial cells, might serve as an inhibitor of breast cancer cell migration.
Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Cadherins; Carcinoma, Intraductal, Noninfiltrating; Cell Adhesion; Cell Line, Tumor; Cell Movement; Epithelial Cells; Female; Humans; Receptors, Cell Surface
PubMed: 33657249
DOI: 10.1111/pin.13087 -
Kindlin-2 in myoepithelium controls luminal progenitor commitment to alveoli in mouse mammary gland.Cell Death & Disease Oct 2023Myoepithelium plays an important role in mammary gland development, but less is known about the molecular mechanism underlying how myoepithelium controls acinus...
Myoepithelium plays an important role in mammary gland development, but less is known about the molecular mechanism underlying how myoepithelium controls acinus differentiation during gestation. Herein, we found that loss of Kindlin-2 in myoepithelial cells impaired mammary morphogenesis, alveologenesis, and lactation. Using five genetically modified mouse lines combined with single-cell RNA sequencing, we found a Kindlin-2-Stat3-Dll1 signaling cascade in myoepithelial cells that inactivates Notch signaling in luminal cells and consequently drives luminal progenitor commitment to alveolar cells identity. Single-cell profiling revealed that Kindlin-2 loss significantly reduces the proportion of matured alveolar cells. Mechanistically, Kindlin-2 depletion in myoepithelial cells promotes Stat3 activation and upregulates Dll1, which activates the Notch pathway in luminal cells and inhibits luminal progenitor differentiation and maturation during gestation. Inhibition of Notch1 with tangeretin allowed luminal progenitors to regain commitment ability in the pregnant mice with Kindlin-2 depletion in myoepithelium. Taken together, we demonstrated that Kindlin-2 is essential to myoepithelium-controlled luminal progenitors to alveoli transition during gestation.
Topics: Animals; Female; Mice; Pregnancy; Cell Differentiation; Epithelial Cells; Epithelium; Lactation; Mammary Glands, Animal
PubMed: 37833248
DOI: 10.1038/s41419-023-06184-2 -
Insect Biochemistry and Molecular... Jul 2023Salivary glands are vital to tick feeding success and also play a crucial role in tick-borne pathogen transmission. In previous studies of Ixodes scapularis salivary...
Salivary glands are vital to tick feeding success and also play a crucial role in tick-borne pathogen transmission. In previous studies of Ixodes scapularis salivary glands, we demonstrated that saliva-producing type II and III acini are innervated by neuropeptidergic axons which release different classes of neuropeptides via their terminals (Šimo et al., 2009b, 2013). Among these, the neuropeptide SIFamide-along with its cognate receptor-were postulated to control the basally located acinar valve via basal epithelial and myoepithelial cells (Vancová et al., 2019). Here, we functionally characterized a second SIFamide receptor (SIFa_R2) from the I. scapularis genome and proved that it senses a low nanomolar level of its corresponding ligand. Insect SIFamide paralogs, SMYamides, also activated the receptor but less effectively compared to SIFamide. Bioinformatic and molecular dynamic analyses suggested that I. scapularis SIFamide receptors are class A GPCRs where the peptide amidated carboxy-terminus is oriented within the receptor binding cavity. The receptor was found to be expressed in Ixodes ricinus salivary glands, synganglia, midguts, trachea, and ovaries, but not in Malpighian tubules. Investigation of the temporal expression patterns suggests that the receptor transcript is highly expressed in unfed I. ricinus female salivary glands and then decreases during feeding. In synganglia, a significant transcript increase was detected in replete ticks. In salivary gland acini, an antibody targeting the SIFa_R2 recognized basal epithelial cells, myoepithelial cells, and basal granular cells in close proximity to the SIFamide-releasing axon terminals. Immunoreactivity was also detected in specific neurons distributed throughout various I. ricinus synganglion locations. The current findings, alongside previous reports from our group, indicate that the neuropeptide SIFamide acts via two different receptors that regulate distinct or common cell types in the basal region of type II and III acini in I. ricinus salivary glands. Our study investigates the peptidergic regulation of the I. ricinus salivary gland in detail, emphasizing the complexity of this system.
Topics: Female; Animals; Ixodes; Salivary Glands; Neurons; Saliva; Neuropeptides
PubMed: 37257628
DOI: 10.1016/j.ibmb.2023.103963 -
Journal of Clinical and Diagnostic... Mar 2015Myoepithelial cells (MEC) are found in the secretory units of many mammalian exocrine glands such as mammary, sweat, lacrimal and salivary glands. They are interposed... (Review)
Review
Myoepithelial cells (MEC) are found in the secretory units of many mammalian exocrine glands such as mammary, sweat, lacrimal and salivary glands. They are interposed between the secretory cells and the basal lamina. Immunohistochemically they are found to contain keratin intermediate filaments and are, therefore, considered to have an epithelial origin but at the same time they contain a large number of myofilaments which represent a massive expression of contractile proteins such as actin, myosin, calponin and caldesmon. Thus have smooth muscle like property also and hence the name. Numerous functions of MEC have been described, the most important of them being important for contraction of the glands and recently it has been found to prevent tumour progression. It should be noted that the diversity in the occurrence and dilemma regarding the pathogenesis of salivary gland tumours is due to lack in uniformity regarding the cells participating in its oncogenesis, especially the MEC. Also proper and extensive studies regarding MEC are very limited and thus have posed difficulty for a pathologist to understand this cell. In this review we try to bring about a thorough description of this cell in both physiological and pathological aspects.
PubMed: 25954719
DOI: 10.7860/JCDR/2015/11372.5707 -
The American Journal of Surgical... Jan 2020Pneumocytic adenomyoepithelioma (PAM) was first described in 2007 and was included in the 2015 World Health Organization Classification of lung tumors as a variant of... (Review)
Review
Pneumocytic adenomyoepithelioma (PAM) was first described in 2007 and was included in the 2015 World Health Organization Classification of lung tumors as a variant of epithelial-myoepithelial tumor. This rare pulmonary neoplasm was reported to show both myoepithelial and duct-like components, with the latter exhibiting pneumocytic differentiation with TTF-1 expression. We present an index case and 6 additional retrospectively identified cases of pulmonary tumors with prototypical features of PAM. However, with additional clinicoradiologic, histologic, immunohistochemical and cytogenetic data, we were able to reclassify them as myoepithelial neoplasms-both primary and metastatic-with entrapped exuberantly hyperplastic alveolar structures lined by TTF-1 pneumocytes. We reviewed the available literature related to PAM and myoepithelial tumors. Our cases suggest that the entity referred to as PAM represents interstitial growth of myoepithelial neoplasms enticing marked proliferation of entrapped pneumocytes rather than a distinct biphasic neoplasm with pneumocytic differentiation.
Topics: Adenomyoepithelioma; Aged; Aged, 80 and over; Alveolar Epithelial Cells; Female; Humans; Lung Neoplasms; Male; Middle Aged; Myoepithelioma; Retrospective Studies
PubMed: 31567188
DOI: 10.1097/PAS.0000000000001376