EMA-

Synonyms: CD227, MUC1, episialin

by Jan Klos

Background

Glycoprotein (encoded by the MUC1 gene in humans) expressed on a luminal surface of most glandular and ductal epithelial cells as well as some hematopoietic cells. It has a protective function by binding to pathogens and also plays a role in a cell signaling capacity ( In the cell nucleus, the protein MUC1 regulates the activity of transcription factor complexes that have a documented role in tumor-induced changes of host immunity). Overexpression, aberrant intracellular localization and changes in glycosylation of this protein have been associated with carcinomas.

Staining in tumors

Majority of adenocarcinomas in various organs, squamous and urothelial carcinomas, renal cell carcinomas, carcinoma of thymus, epithelioid sarcoma, synovial sarcoma, chordoma, DSRCT, perineurioma, choriocarcinomas, mesotheliomas (mainly epithelioid type, but also in about 30% of sarcomatoid type), desmoplastic nested spindle cell tumor of  liver,  NUT  midline carcinoma, meningioma, dendritic cell sarcomas, some gliomas, some lymphomas including ALCL, minority of myoepithelial tumors

Gonadal sex-cord stromal tumors, germ cell tumors (except choriocarcinoma), melanoma, solitary fibrous tumor, adrenal cortical carcinoma, hepatocellular carcinoma,  ……. are negative………..

Staining pattern

Staining pattern is membranous.

Control tissue

Tonsil (majority of intermediate and superficial squamous epithelial cells showing  at least moderate cytoplasmic staining and predominantly membranous staining of the plasma cells).

Application

Nonspecific marker which however commonly expressed, should not be used alone as lineage marker for epithelial cells!

  • Marker of meningioma
  • Marker of mammary and extramammary Paget disease
  • Marker of micropapillary carcinoma in different organs, where it gives characteristic staining pattern being positive on basal (stroma-facing) surface of the cells clusters
  • Helps to distinguish systemic anaplastic large cell lymphoma (ALCL) (40% of ALK-ve and >90% ALK+ve cases, where sometimes positive staining is seen only on a proportion of tumor cells) from cutaneous anaplastic large cell lymphoma (usually negative)
  • Stains positive plasma cells and plasmablastic proliferations including rare ALK+ large B-cell lymphoma (ALK+LBCL)
  • Gives strong, membranous staining in malignant mesothelioma (mostly in epithelioid variants), while benign mesothelial proliferations are negative or weakly positive

Selected references

  1. Doyle LA, Fletcher CD. EMA positivity in epithelioid fibrous histiocytoma: a potential diagnostic pitfall.J Cutan Pathol. 2011 Sep;38(9):697-703. doi: 10.1111/j.1600-0560.2011.01747.x. Epub 2011 Jul 14.PMID: 21752057
  2. https://en.wikipedia.org/wiki/MUC1
  3. Kuan SF1, Montag AG, Hart J, et al. Differential expression of mucin genes in mammary and extramammary Paget’s disease. Am J Surg Pathol. . 2001 Dec;25(12):1469-77.  doi: 10.1097/00000478-200112000-00001. PMID: 11717535  DOI: 10.1097/00000478-200112000-00001
  4. WHO Classification of Tumours of Hematopoietic and Lymphoid Tissue ed 2017