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Epithelial Membrane Antigen (EMA)

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 9 May 2012, last major update May 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.


● Also called CD227, MUC1 and episialin
● Large cell surface mucin glycoprotein expressed by most glandular and ductal epithelial cells and some hematopoietic cells


● 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 Pagetís 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)

Micro images

Bladder: high grade urothelial carcinoma

Breast / bladder micropapillary carcinoma: EMA/MUC1 shows reverse polarity staining pattern

Cervix: adenoid cystic carcinoma

CNS: meningioma is EMA+: Fig 4 (right)

CNS: meningioma; left-chordoid; middle-clear cell; right-ear / temporal bone

CNS: papillary ependymoma

Colorectum: micropapillary carcinoma

Colon: perineurioma of perineum (fig 4)

Extrahepatic bile duct carcinoma

Heart: synovial sarcoma

Kidney: mucinous tubular and spindle cell carcinoma

Kidney: papillary carcinoma - left-type 1; right-solid variant

Kidney: renal cell carcinoma

Liver: metastatic renal cell carcinoma (fig A)

Lung adenocarcinoma with micropapillary pattern

Lymphoma: anaplastic large cell (fig B in both images)

Pancreas: IPMN, intestinal type is MUC1 negative

Pancreas: micropapillary carcinoma has MUC1 staining of the stroma-facing surface of cell clusters

Pancreas: MUC1 staining on apices of papillae associated with neutrophils; left-mucinous cystic neoplasm with papillary in-situ carcinoma; right-intraductal papillary mucinous neoplasm

Pancreas: PanIN and ductal adenocarcinoma

Salivary glands: clear cell carcinoma, hyalizing subtype (fig C)

Scrotum: epithelioid sarcoma

Soft tissue: parachordoma

Thymic carcinoma (fig g)

Urothelial tract: micropapillary carcinoma versus urothelial carcinoma

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
● Pagetís 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

J Leukoc Biol 2002;72:692

End of Stains > Epithelial Membrane Antigen (EMA)

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