Stains
Epithelial membrane antigen (EMA)

Author: Nat Pernick, M.D. (see Authors page)

Revised: 1 August 2018, last major update May 2012

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Epithelial membrane antigen [title]

Cite this page: Pernick, N. Epithelial membrane antigen (EMA). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsema.html. Accessed August 18th, 2018.
Definition / general
  • Also called CD227, MUC1 and episialin
  • Large cell surface mucin glycoprotein expressed by most glandular and ductal epithelial cells and some hematopoietic cells
Pathophysiology
  • Normally acts as barrier to apical surface of epithelial cells, playing a protective and regulatory role
  • Inhibits formation of E-cadherin / beta catenin complex
  • Micropapillary carcinoma may be due to reversal in cell polarity of MUC1, changing from apical surface (normal) to stroma-facing surface (micropapillary carcinoma, Mod Pathol 2004;17:1045)
  • Partial reverse cell polarity may identify breast carcinomas that represent part of spectrum of invasive micropapillary carcinoma but lack its morphology (Am J Surg Pathol 2010;34:1637)
  • Reactive gastropathy associated with loss of MUC1 expression in 67% of cases, may play a role in development of its serrated profile (Arch Pathol Lab Med 2007;131:86)
Clinical features
  • Highly expressed by most adenocarcinomas, associated with poor prognosis (Hum Pathol 1995;26:432)
  • In breast cancer, aberrant cytoplasmic and membranous localization (associated with micropapillary subtype) is associated with poor outcome (Mod Pathol 2005;18:1295)
  • Shed into the bloodstream of adenocarcinoma patients, used in commercial serum tumor marker assays (CA15-3)
Uses by pathologists
  • Common epithelial marker
  • Marker of meningioma
  • Marker of Paget disease (Am J Surg Pathol 2001;25:1469)
  • In breast and bladder micropapillary carcinoma, MUC1 stains stroma-facing surface of cell clusters (basal), which accentuates outlines of micropapillary units to form a distinct band on this surface
  • Distinguish systemic anaplastic large cell lymphoma (MUC1+) from cutaneous anaplastic large cell lymphoma (usually MUC1-, Am J Surg Pathol 2008;32:1421)
Microscopic (histologic) images

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Bladder, high grade urothelial carc

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Cervix, adenoid cystic carcinoma

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Heart, synovial sarcoma

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Kidney, papillary carcinoma, solid


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Pancreas, IPMN, intestinal, MUC1-

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Scrotum, epithelioid sarcoma

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Soft tissue, parachordoma



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CNS, meningioma, EMA+, F4

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Colon, perineurioma of perineum, F4

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Pancreas, micropapillary carcinoma

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Pancreas, MUC1 staining



Positive staining - normal
  • Apical surface of almost all glandular and ductal epithelial cells including breast (and Toker cells), kidney distal tubules, lung (type II pneumocytes), pancreas, salivary glands, skin (eccrine and apocrine glands)
  • Activated T cells, some B cells, monocytes, follicular dendritic cells and perineurial cells
Positive staining - disease
  • Adenocarcinomas (breast, colorectal, pancreatic, other)
  • Carcinoid tumor, chordoma
  • Choriocarcinoma
  • Desmoplastic small round cell tumor
  • Epithelioid sarcoma
  • Follicular dendritic cell sarcoma, interdigitating dendritic cell / reticulum cell sarcoma
  • Lung: type II pneumocyte lesions (type II cell hyperplasia, dysplastic type II cells, apical alveolar hyperplasia)
  • Lymphoma: anaplastic large cell, diffuse large B cell (variable), plasmablastic, primary effusion
  • Meningioma
  • Mesotheliomas (epithelioid)
  • Myeloma
  • Paget’s disease
  • Perineurioma
  • Plasmacytomas
  • Renal cell carcinoma
  • Synovial sarcoma (epithelial areas)
  • Thymic carcinoma (often)
Negative staining
  • Myoepithelial cells
  • Adrenal and hepatocellular carcinoma, germ cell tumors (except choriocarcinoma)
  • Acquired cystic disease associated renal cell carcinoma
  • Leiomyosarcoma (usually), liposarcoma
  • Melanoma
  • Neuroblastoma
  • Paraganglioma
  • Solitary fibrous tumor
Additional references