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      MUC-1 expression in pleomorphic adenomas using two human milk fat globule protein membrane antibodies (HMFG-1 and HMFG-2)

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          Abstract

          Pleomorphic adenoma (PA) is the most common salivary gland tumor and its microscopic features and histogenesis are a matter of debate. Human milk fat globule protein membrane (HMFG) monoclonal antibodies (MoAbs) comprise a set of antibodies against the mucin 1 (MUC-1) protein detected in several salivary gland tumors.

          Objective

          The aim of this study was to assess the immunoexpression of the PA neoplastic cells to MUC-1 protein using HMFG-1 and HMFG-2 MoAbs, contrasting these results with those from normal salivary gland tissue.

          Material and Methods

          Immunohistochemical detection of MUC-1 protein using HMFG-1 and HMFG-2 MoAbs was made in 5 mm thick, paraffin embedded slides, and the avidin-biotin method was used.

          Results

          Positivity to HMFG-1 and HMFG-2 MoAbs was found in ductal, squamous metaplastic and neoplastic myoepithelial cells, keratin pearls and intraductal mucous material. Two kinds of myoepithelial cells were identified: classic myoepithelial cells around ducts were negative to both MoAbs, and modified myoepithelial cells were positive to both MoAbs. This last cellular group of the analyzed tumors showed similar MUC-1 immunoexpression to ductal epithelial cells using both HMFG antibodies. Intraductal mucous secretion was also HMFG-1 and HMFG-2 positive.

          Conclusions

          Our results showed there are two kinds of myoepithelial cells in PA. The first cellular group is represented by the different kinds of neoplastic myoepithelial cells and is HMFG-positive. The second one is HMFG-negative and represented by the neoplastic myoepithelial cells located around the ducts.

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          Most cited references53

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          Monoclonal antibodies to epithelium-specific components of the human milk fat globule membrane: production and reaction with cells in culture.

          W Bodmer, J Burchell, J. Arklie … (1981)
          Three hybridomas producing monoclonal antibodies (IgG), reacting with components of the human mammary milk fat globule have been isolated. When tested for binding to a wide range of human cell lines and strains, all three antibodies show negative reactions with fibroblasts, lymphoblastoid cells, and a large number of epithelial cell lines of non-breast origin. Two of the antibodies (1.10.F3 and 3.14.A3) reacted with seven out of eight breast cancer lines tested, and with epithelial cells cultured from human milk. The other antibody (3.15.C3) reacted with only two of the breast cancer cell lines.
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            Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma.

            Susana A. Ribeiro, Sarki Abdulkadir, J. GONCALVES FILHO … (2002)
            Polymorphous low-grade adenocarcinoma of the minor salivary glands is an infiltrative neoplasm characterized by bland-looking tumour cells arranged in diverse architectural patterns. It is considered to be of low-grade malignant potential in that nodal metastases are seen in only a minority, and distant spread is rare. Even more unusual is the transformation of polymorphous low-grade adenocarcinoma to a histologically high-grade carcinoma, i.e. dedifferentiation. In this paper, we describe the clinicopathological and immunohistochemical findings in two further examples. Two patients presented each with a tumour of the palate. Histopathological examination showed the typical morphological, cytological and immunohistochemical features of a polymorphous low-grade adenocarcinoma. In one case there was a second component of high-grade carcinoma showing nuclear atypia, markedly increased mitotic activity and MIB1 index, as well as prominent zones of necrosis. It expressed epithelial markers and androgen receptors, and thus resembled salivary duct carcinoma. Similar tumour tissue was observed in one of the cervical nodal metastases, which was biopsied at the same time as the palate. In the second patient, a high-grade component was discovered when the tumour recurred in the palate 13 years after the initial biopsy. Whilst morphologically similar to that in first case, there were significant immunohistochemical differences such as retention of some of the polymorphous low-grade adenocarcinoma profile and absence of androgen receptor expression. Polymorphous low-grade adenocarcinoma was first described relatively recently, and as experience with it continues to accumulate, it is becoming clear that late recurrences and metastases, whilst still infrequent, may not be quite as rare as previously thought. Reports of histological transformation are even scarcer, and most occurred at least 13 years after the polymorphous low-grade adenocarcinoma was initially recognized. It is a real possibility that this phenomenon, like clinical progression, may also be encountered more often as time passes. Therefore, we believe that, whilst polymorphous low-grade adenocarcinoma is certainly far less aggressive than, for example, adenoid cystic carcinoma, it nevertheless remains a true malignancy with a potential to prove fatal in a minority of patients.
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              Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers.

              J. Arklie, J Taylor-Papadimitriou, W. BODMER … (1981)
              Two monoclonal antibodies, 3.14.A3 and 1.10.F3, raised against a delipidated preparation of the human milk fat globule and characterized as epithelium-specific (Taylor-papadimitriou et al., 1981) were assayed histologically, by an indirect immunoperoxidase technique, against formalin-fixed, paraffin-embedded, normal and tumour tissue sections, in order to establish their in vivo specificity. Both antibodies bound to less than 10% of the alveoli and ducts in the resting breast, but bound to all areas of alveoli, ducts and secretion in the lactating breast. Binding was to the luminal surface of the alveolar and ductal epithelium. Antibody 3.14.A3 showed positive reactions with each of 20 primary breast carcinomas tested, and with metastatic lesions in lymph nodes from six of these. Antibody 1.10.F3 also reacted with most of the primary carcinomas but not with those of the mucoid type nor with metastatic lesions in lymph nodes. When tested against a variety of normal tissues, 1.10.F3 bound only to the luminal epithelial surface of classically defined exocrine glands, to their associated ducts and to the collecting tubules of kidney and bronchioles of the lung. 3.14.A3 showed a similar pattern of binding to 1.10.F3 but also bound to sweat glands, the alveolar epithelium of lung and the luminal epithelium of the ductuli efferentes of the epididymis. The only tumours, other than breast, showing a positive reaction with the antibodies were adenocarcinomas of the lung, uterus and ovary.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Appl Oral Sci
                Journal ID (iso-abbrev): J Appl Oral Sci
                Title: Journal of Applied Oral Science
                Publisher: Faculdade de Odontologia de Bauru da Universidade de São Paulo
                ISSN (Print): 1678-7757
                ISSN (Electronic): 1678-7765
                Publication date (Print and electronic): May-Jun 2015
                Publication date (Print): May-Jun 2015
                Volume: 23
                Issue: 3
                Pages: 265-271
                Affiliations
                [1]Clinical Oral Pathology Laboratory. División de Estudios de Posgrado e Investigación. Facultad de Odontología, Universidad Nacional Autónoma de México, México, D.F. - México.
                Author notes
                Corresponding address: Constantino Ledesma-Montes - Ciprés #169-2 - Col. Vergel-Coapa - México - D.F. - 14320 - México - Phone/Fax: +52 55-5671-1389 - e-mail: cledezma@ 123456unam.mx
                Article
                Publisher ID: 1678-775720140481
                DOI: 10.1590/1678-775720140481
                PMC ID: 4510660
                PubMed ID: 26221920
                SO-VID: e532f5e1-ee9b-4508-af72-45d0771cc813
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 26 November 2014
                Date revision received : 28 January 2015
                Date accepted : 23 March 2015
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 28, Pages: 7
                Categories
                Subject: Original Articles

                Keywords: salivary gland tumors,pleomorphic adenoma,muc-1 mucin,human milk fat globule membrane,myoepithelial cell
                Data availability:
                Keywords: salivary gland tumors, pleomorphic adenoma, muc-1 mucin, human milk fat globule membrane, myoepithelial cell

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