MUC1

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

Images

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

• https://twitter.com/JustineVarinot/status/816616480578146304

Functions

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

Pathology

 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)

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

• anaplastic large cell lymphoma (ALCL)
• diffuse large B-cell lymphoma (variable) (DLBCL)
• Hodgkin lymphoma with nodular lymphocytic predominance (+/-)
• plasmablastic lymphoma
• primary effusion lymphoma
• myeloma
• plasmacytoma

 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)

Biomarker

 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