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MIM.158340 1q21

Monday 23 August 2004

mucin-1, epithelial membrane antigen, EMA; CD227, MUC1 and episialin


Definition: Large cell surface mucin glycoprotein expressed by most glandular and ductal epithelial cells and some hematopoietic cells.

It is a transmembrane protein normally expressed in glandular or luminal epithelial cells and hematopoietic cells and absent in skin epithelium and mesenchymal cells.


- Normal

  • Localized to the apical membranes and provides barrier function.

- Abnormal

  • Overexpressed and loses cell polarity
  • Redistributed in cell surface and cytoplasm
  • Membranous staining: mesothelioma cells
  • Cytoplasmic staining: carcinoma cells
  • Apical luminal membrane staining can also be observed
  • Dot-like / ring-like staining pattern in ependymal cells


- Invasive micropapillary carcinoma of the breast and its reversed apical pattern of MUC1 expression


- Normally acts as barrier to apical surface of epithelial cells, playing a protective and regulatory role
- Inhibits formation of E-cadherin - beta-catenin complex

Diagnostic use

- Highly expressed by most carcinomas (especially adenocarcinomas) and hematologic cancers.

- Common epithelial marker, commonly used alongside other cytokeratin stains

- Marker of Paget disease
- Partial reverse cell polarity (prominent linear EMA reactivity with decreased cytoplasmic staining) may identify breast carcinomas that represent part of the spectrum of invasive micropapillary carcinoma but lack its morphology

- Distinguishes

- Reverse polarity

  • Lung : Micropapillary carcinoma may be due to reversal in cell polarity of MUC1, changing from apical surface (normal) to stroma-facing surface
  • partial reverse cell polarity may identify breast carcinomas that represent part of spectrum of invasive micropapillary carcinoma but lack its morphology

- 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)

Expression in tumors

- adenocarcinomas

  • Highly expressed by most adenocarcinomas
  • associated with poor prognosis (Hum Pathol 1995;26:432)
  • Shed into the bloodstream of adenocarcinoma patients, used in commercial serum tumor marker assays (CA15-3)

- mammary carcinomas

  • In breast cancer, aberrant cytoplasmic and membranous localization (associated with micropapillary subtype) is associated with poor outcome (Mod Pathol 2005;18:1295)

- meningioma
- Paget disease (Am J Surg Pathol 2001;25:1469)
- Hodgkin lymphoma with nodular lymphocytic predominance (Popemma paragranuloma)

  • Popcorn cell can be EMA+

- 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)

- Lymphomas

- meningioma
- mesotheliomas (epithelioid mesothelioma - peripheral positivity)

- Paget’s disease
- perineurioma
- renal cell carcinoma
- synovial sarcoma (epithelial areas)
- thymic carcinoma (often)

Negative tumors

- Myoepithelial cells
- adrenal cortical carcinoma
- hepatocellular carcinoma
- germ cell tumors (except choriocarcinoma)
- acquired cystic disease associated renal cell carcinoma
- leiomyosarcoma (usually), liposarcoma
- melanoma
- neuroblastoma
- paraganglioma
- solitary fibrous tumor

Diagnostic use

- 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)

Prognostic use

- Increased expression is associated with poor prognosis of most carcinomas, including those involving breast, cervical, pancreatic, colorectal


- MUC1 / Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma. (27481516)

Open references

- Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma. Lappi-Blanco E, Mäkinen JM, Lehtonen S, Karvonen H, Sormunen R, Laitakari K, Johnson S, Mäkitaro R, Bloigu R, Kaarteenaho R.
Tumour Biol. 2016 Oct;37(10):13811-13820.
PMID: 27481516