p63: A Novel Myoepithelial Cell Marker in Canine Mammary Tissues

2003 ◽  
Vol 40 (4) ◽  
pp. 412-420 ◽  
Author(s):  
A. Gama ◽  
A. Alves ◽  
F. Gartner ◽  
F. Schmitt

Several immunohistochemical markers have been used to demonstrate the presence of myoepithelial cells in order to determine their role in the histogenesis of mammary tumors. p63, a recently characterized p53 homologue, is consistently expressed in myoepithelial cells of the human breast; however, no assessment of its immunoreactivity has been reported so far in canine mammary tissues. We investigated p63 immunohistochemical expression, as a novel myoepithelial cell nuclear marker, in 81 samples of normal ( n = 2), hyperplastic ( n = 11), and neoplastic ( n = 68) canine mammary tissues. Myoepithelial phenotype was confirmed by using complementary monoclonal antibodies: alpha-smooth muscle actin, cytokeratin 14, cytokeratin AE1/AE3, and vimentin. p63 expression was observed in 91.4% (74/81) of the samples evaluated. Normal mammary glands, mammary hyperplasias, and benign tumors showed 100% immunoreactivity, with p63 expression restricted to myoepithelial cell nuclei. In general, benign mixed tumors showed a basal cell compartment immunoreactive to p63, with a gradual decrease of its expression during myoepithelial transformation. p63 expression was found in 72% of malignant tumors, allowing myoepithelial or basal cell identification in spindle-cell carcinomas (2/2), tubulopapillary carcinomas (8/9), solid carcinomas (7/10), and carcinosarcomas (1/3). The osteosarcoma analyzed was p63 negative. In our series, stromal components were consistently nonreactive to p63. In conclusion, the present study reveals p63 as a sensitive and highly specific marker of myoepithelial cells in canine mammary tissues, and the authors suggest p63 as an additional marker for defining myoepithelial histogenesis.

2001 ◽  
Vol 125 (2) ◽  
pp. 232-236
Author(s):  
Lori Soma ◽  
Virginia A. LiVolsi ◽  
Zubair W. Baloch

Abstract Objective.—CD34-positive dendritic interstitial cells may be associated with the regulation of tumor growth. This association has been studied in various human neoplasms, especially skin tumors. In this study, we evaluated the distribution of dendritic interstitial cells and myofibroblastic cells at the tumor periphery of various benign and malignant salivary gland neoplasms. Methods.—Forty-nine cases of salivary gland tumors were selected: 16 pleomorphic adenomas, 12 Warthin tumors, 8 polymorphous low-grade tumors, 5 adenoid cystic carcinomas, 6 acinic cell carcinomas, and 2 mucoepidermoid carcinomas. Immunohistochemical analysis was performed by using antibodies for CD34 (dendritic cells) and α-smooth muscle actin (myofibroblast) on formalin-fixed, paraffin-embedded archival tissue. Staining intensity was graded as marked (3+), moderate (2+), weak (1+), and absent (0). Results.—Staining intensity for CD34 was 3+ in 24 (86%) of 28 benign tumors (pleomorphic adenomas and Warthin tumors) and 6 (29%) of 21 malignant tumors (polymorphous low-grade tumors, acinic cell carcinomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas) and 2+ in 4 (19%) of 21 malignant tumors. None of the benign tumors displayed 2+ staining with CD34. Three (11%) of 28 benign and 11 (52%) of 21 of malignant tumors failed to stain with CD34. α-Smooth muscle actin staining was 3+ in 10 (36%) of 28 benign tumors and 6 (29%) of 21 malignant tumors, and 2+ in 11 (39%) of 28 benign and 2 (9%) of 21 malignant tumors. Five (18%) of 28 benign and 11 (52%) of 21 malignant tumors failed to stain with α-smooth muscle actin. Conclusion.—We conclude that the dendritic interstitial cells and myofibroblastic cells may be associated with the regulation of tumor growth in salivary gland tumors.


2019 ◽  
Vol 56 (4) ◽  
pp. 526-535
Author(s):  
Ángela Alonso-Diez ◽  
Antonio Ramos ◽  
Paola Roccabianca ◽  
Lucía Barreno ◽  
Mª Dolores Pérez-Alenza ◽  
...  

Canine spindle cell mammary tumor (CSCMT) is an infrequent canine mammary tumor (CMT) composed of spindle or fusiform cells, which represents a challenge for pathologists and clinicians. Mammary tumors submitted for histopathology from 1998 to 2013 and compatible with CSCMTs were retrospectively selected. The tumors were diagnosed based on the hematoxylin and eosin (HE)–stained section; malignant tumors were graded using a canine soft tissue sarcoma grading scheme and a canine mammary tumor grading scheme, and they were further assigned a diagnosis based on immunohistochemistry (IHC) for pancytokeratin, cytokeratin 14, p63, calponin, vimentin, Ki-67, CD31, desmin, myosin, smooth muscle actin, glial fibrillary acidic protein, and S-100. The origin of the tumors was assessed as mammary, skin, or unknown. The prevalence of CSCMT was 1% of all CMTs. CSCMTs included 3 benign tumors (1 angioma and 2 benign myoepitheliomas) and 67 malignant tumors that after IHC were diagnosed as malignant myoepithelioma (64%), carcinoma and malignant myoepithelioma (19%), hemangiosarcoma (8%), undifferentiated sarcoma (5%), peripheral nerve sheath tumor (3%), and fibrosarcoma (2%). The diagnosis based on the HE-stained section differed from the diagnosis after IHC in 75% of the malignant cases. The majority of malignant CSCMTs were solitary (57%) large tumors (6.42 ± 3.92 cm) with low metastatic potential and high survival rate (8% tumor-related mortality). Higher sarcoma grade was associated with older age ( P = .034) and greater tumor size ( P = .037). Malignant CSCMTs need to be evaluated by IHC to ensure the histotype and the relatively benign clinical behavior, despite their large size.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Rino Frisina ◽  
Francesco Tessarolo ◽  
Ivan Marchesoni ◽  
Federico Piccoli ◽  
Emiliana Bonomi ◽  
...  

Proliferative membranes of fibrocontractive retinal disorders are extensively studied from the morphological and evolutive point of view. Despite this, little is known of their cellular composition. In this study, the authors investigated the morphological characteristics and cell composition of various types of surgically excised proliferative membranes and internal limiting membranes (ILMs), in order to provide new data supporting or challenging the pathogenic theories proposed until now. Sixty-nine specimens from 64 eyes of 64 consecutive patients were collected at surgery and subjected to a multilevel analysis by means of optical and electron microscopy. Membrane samples were semiquantitatively evaluated for the amount and distribution of cell nuclei and pigment. Immunohistochemical staining was performed with antibodies to alpha smooth muscle actin and CD68. Data were analyzed after grouping according to the following tissue types: ILM (20 specimens), epiretinal membrane (ERM) (22 specimens), ILM + ERM (20 specimens), and proliferative vitreoretinopathy (PVR) (7 specimens). The cell components found in the ERM specimens, like myofibroblasts, macrophages, and polymorphonuclear cells, were recognized as the expression of cell migration and differentiation that induced an inflammatory process and a fibroproliferative repair process. The detection of pigments in specific types of ERM, like those associated with lamellar macular hole (LMH) or secondary to retinal detachment (RD), diabetes, and PVR, suggested that retinal pigment epithelium (RPE) cells may have a role in the development of these vitreoretinal disorders. The reduction of the ERM cellularity with the patient’s age supports the hypothesis that ERM evolves in time up to a fibrous tissue formation.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Germana Beha ◽  
Giuseppe Sarli ◽  
Barbara Brunetti ◽  
Francesco Sassi ◽  
Domenico Ferrara ◽  
...  

Myoepithelium is present in canine mammary tumors as resting and proliferative suprabasal and spindle and stellate interstitial cells. The aim of this paper was to evaluate a panel of markers for the identification of four different myoepithelial cell morphological types in the normal and neoplastic mammary gland and to investigate immunohistochemical changes from an epithelial to a mesenchymal phenotype. Cytokeratin 19 (CK19), cytokeratin 5/6 (CK5/6), cytokeratin 14 (CK14), estrogen receptor (ER), p63 protein, vimentin (VIM), andα-smooth muscle actin (Alpha-SMA) antibodies were used on 29 neoplasms (3 benign and 3 malignant myoepithelial tumors, 7 carcinomas in benign-mixed tumors and 16 complex carcinomas) and on normal tissue of mammary glands. All these antibodies were also tested on 3 mammary tissues from animals with no mammary pathology. The myoepithelial markers were well expressed in the suprabasal cells and gradually lost in the motile types, with the stellate cells maintaining only VIM expression typical of mesenchyma. ER labeled some resting and motile myoepithelial cells. On the basis of our results, we propose a transition from myoepithelial immotile cells into migratory fibroblast-like cells. This transition and the characterization of an immunohistochemical panel for resting and motile myoepithelial cells shed more light on the biological behavior of myoepithelial cells.


2010 ◽  
Vol 33 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Ioulia Chatzistamou ◽  
Nikolina Dioufa ◽  
George Trimis ◽  
Alexandra Sklavounou ◽  
Christos Kittas ◽  
...  

Background: Concerted alterations between stromal fibroblasts and neoplastic cells underline the carcinogenic process. Activation of alpha-smooth muscle actin (SMA) expression, a cytoskeleton protein normally expressed only in myoepithelial cells, is considered a landmark for the activation of stromal fibroblasts with little however being known regarding the mechanism governing the expression of SMA in the stroma.Methods: We have evaluated by immunohistochemistry the expression of SMA in the stroma of oral malignant and pre-malignant lesions, in association with the expression of p53 and p21 tumor suppressors that were shown previously to be deregulated and/or mutated in stromal fibroblasts of various cancers. The effects of p21 knockdown in SMA expression and cell migration and the mRNA levels of endogenous p21 in fibroblasts co-cultured with cancer cells were also assessed.Results: We found that both p21 and SMA expression was elevated in the stroma, but not the epithelium, of malignant as compared to pre-malignant lesions. We also noted that the expression of both was positively correlated, implying that SMA expression may be regulated by p21. Consistently with this notion we found that siRNA-mediated p21 suppression resulted in the reduction of SMA levels and also inhibited cell migration.Conclusion: Our results show that p21 deregulation is associated with the activation of stromal fibroblasts of oral cancers by a mechanism that involves the stimulation of SMA expression.


1997 ◽  
Vol 8 (4) ◽  
pp. 604-615 ◽  
Author(s):  
A Clayton ◽  
R Steadman ◽  
J D Williams

Progressive renal disease is frequently accompanied by renal interstitial inflammation and fibrosis in which the activity of resident fibroblasts may be of central importance. Because there are relatively few fibroblasts in the normal cortical interstitium and there is no specific marker to permit their identification, these cells have proved difficult to characterize in vitro. In this study, these cells were isolated and established in culture, using CD90 as a positive selection marker. Antibodies to CD90 bound to tubular epithelial cells and fibroblasts, but not to glomerular cells in kidney sections. In culture, only fibroblasts were CD90-positive. These normal renal cortical fibroblasts (RCF) were alpha-smooth muscle actin- and vimentin-positive, but desmin-, cytokeratin-, and factor VIII-negative, identifying them as myofibroblasts. They expressed platelet-derived growth factor alpha and beta receptors; CD44; and alpha 2, beta 1, and beta 3 integrin chains: this combination of markers was also characteristic of fibroblasts in sections of normal cortex. These cells were positive for ICAM-1 but negative for VCAM-1. Similarly, proliferating or growth-arrested renal cortical fibroblasts (RCF) in culture expressed ICAM-1 but not VCAM-1. The expression of VCAM-1 was detected, however, and that of ICAM-1 was increased on fibroblasts associated with inflammatory infiltrates in sections from fibrotic kidneys, and ICAM-1 and VCAM-1 were up-regulated on RCF in culture after incubation with increasing doses of interleukin-1 beta or tumor necrosis factor alpha (maximum between 24 and 48 h). These adhesion molecules were functional, and neutrophils adhered to resting and cytokine-activated RCF. Binding was maximal between 24 and 48 h after cytokine treatment and was inhibited by anti-CD18 antibodies. ICAM-1 is the principal adhesion molecule controlling inflammatory cell infiltration of the interstitium. The study presented here suggests that cortical fibroblasts may be central to the control of this infiltration.


1999 ◽  
Vol 112 (12) ◽  
pp. 1925-1936
Author(s):  
M. Schon ◽  
J. Benwood ◽  
T. O'Connell-Willstaedt ◽  
J.G. Rheinwald

We have characterized precisely the cytokeratin expression pattern of sweat gland myoepithelial cells and have identified conditions for propagating this cell type and modulating its differentiation in culture. Rare, unstratified epithelioid colonies were identified in cultures initiated from several specimens of full-thickness human skin. These cells divided rapidly in medium containing serum, epidermal growth factor (EGF), and hydrocortisone, and maintained a closely packed, epithelioid morphology when co-cultured with 3T3 feeder cells. Immunocytochemical and immunoblot analysis disclosed that the cells differed from keratinocytes in that they were E-cadherin-negative, vimentin-positive, and expressed an unusual set of cytokeratins, K5, K7, K14, and K17. When subcultured without feeder cells, they converted reversibly to a spindle morphology and ceased K5 and K14 expression. Under these conditions, EGF deprivation induced flattening, growth arrest, and expression of alpha-smooth muscle actin ((α)-sma). Coexpression of keratins and alpha-sma is a hallmark of myoepithelial cells, a constituent of secretory glands. Immunostaining of skin sections revealed that only sweat gland myoepithelial cells expressed the same pattern of keratins and alpha-sma and lack of E-cadherin as the cell type we had cultured. Interestingly, our immunocytochemical analysis of ndk, a skin-derived cell line of uncertain identity, suggests that this line is of myoepithelial origin. Earlier immunohistochemical studies by others had found myoepithelial cells to be K7-negative. We tested five K7-specific antibodies that can recognize this protein in western blots and in the assembled keratin filaments of mesothelial cells. Three of these antibodies did not recognize the K7 present in myoepithelial cell filaments or in HeLa cell filaments, indicating that some K7 epitopes are masked when K7 pairs with K17 instead of with its usual keratin filament partner, K19.


1970 ◽  
Vol 1 (1) ◽  
pp. 9-12 ◽  
Author(s):  
P Lavaju ◽  
SK Arya ◽  
A Sinha ◽  
S Pandey ◽  
S Adhikari ◽  
...  

Background: Ocular tumors are commonly encountered in ophthalmic practice. Objective: To study the clinical pattern of ocular tumors in the eastern region of Nepal. Materials and methods: The hospital records of patients with ocular tumors treated at B P Koirala Institute of Health Sciences in the eastern region of Nepal over a period of 5 years (April 2003 - March 2008) were studied retrospectively. Results: Of 115 consecutive patients with ocular tumors, 40 (34.75%) were below the age of 21 years, 41 (35.65%) were in the age group of 21-50 years and 34 (29.56%) of age above 50 years. There were 48 (41.73%) and 67 (58.26%) patients with benign and malignant tumors respectively. The common benign tumors were conjunctival papilloma, dermoid cysts, nevus, cystic lesions and hemangioma. Among the malignant tumors, basal cell carcinoma was the commonest (22.38%). Retinoblastoma was the most common ocular malignant tumor in the pediatric age group (88.8%). Basal cell carcinoma was the commonest eyelid malignancy 53.57%. Conclusion: Conjunctival papilloma, dermoid cysts, nevus, cystic lesions and hemangioma are common benign ocular tumors, whereas basal cell carcinoma and retinoblastoma are the commonest ocular malignancies in adults and children respectively. Key words: ocular malignancy; retinoblastoma; basal cell carcinoma DOI: 10.3126/nepjoph.v1i1.3667 Nep J Oph 2009;1(1):9-12


2002 ◽  
Vol 39 (2) ◽  
pp. 247-256 ◽  
Author(s):  
A. Espinosa de los Monteros ◽  
M. Y. Millán ◽  
J. Ordás ◽  
L. Carrasco ◽  
C. Reymundo ◽  
...  

The immunohistochemical expression of the smooth muscle-specific protein calponin was studied to assess the contribution of myoepithelial cells to the histogenesis of spindle cells of complex and mixed tumors of the mammary gland of the dog and the origin of cartilage and bone in mixed tumors. Formalin-fixed tissues from 55 benign and malignant tumors (49 also containing surrounding normal mammary gland) were evaluated. Periacinar and periductal myoepithelial cells of all the 49 normal mammary glands were diffusely stained by the anti-human calponin monoclonal antibody. Calponin was found in 53 (98%) of the tumors studied, reacting with the myoepithelium-like cells of 86% of benign tumors and their remnants in 85% of malignant tumors. Five different types of calponin-immunoreactive myoepithelial cells were identified: hypertrophic myoepithelial cells, fusiform cells, stellate myoepithelial cells, rounded (myoepithelial) cells, and chondroblasts. Differences in staining intensity and staining pattern among these five types of cells suggested a transition of myoepithelial cells to chondroblasts. Stromal myofibroblasts also showed calponin immunoreactivity, but they did not react with a cytokeratin 14 monoclonal antibody, which recognizes myoepithelial cells in mammary gland. Calponin appears to be a very sensitive marker of normal and neoplastic myoepithelium in the canine mammary gland, and its identification in different cell types of complex and mixed tumors of the mammary gland of the dog suggests a major histogenetic role for myoepithelial cells.


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