Synonyms: Mucin 4
by Jan Klos
Background
MUC4 (encoded by the MUC4 gene in humans) is a glycoprotein of high molecular weight that plays various roles in the progression of cancer, mainly due to its signaling and anti-adhesive properties that contribute to tumor development and metastasis.
Staining in normal cells:
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Staining in tumors
MUC4 is overexpressed in many carcinomas and only few mesenchymal tumors. Malignant mesothelioma regardless subtype is usually negative.
Staining pattern
Is cytoplasmic often with accentuated membranes.
Application
- In diagnostic surgical pathology MUC4 is used as a sensitive marker of low-grade fibromyxoid sarcoma (LGFMS) and its subtype hyalinizing spindle cell tumor with giant rosettes, both characterized by the same chromosomal translocation (FUS gene on chromosome 16 involving CREB3L2 on chromosome 7 as fusion partner).
- Among mesenchymal tumors MUC4 is also expressed in majority of biphasic synovial sarcoma and sclerosing epithelioid fibrosarcoma, each showing specific genetic aberrations.
- Only few cases of CIC-arranged sarcoma are reported positive.
- Positive staining in many carcinomas can be used in differential diagnosis against mesothelioma where positive staining speaks strongly for carcinoma, but negative result of staining is usually inconclusive.
Selected references
- Doyle LA, Möller E, Dal Cin P, et al. MUC4 is a highly sensitive and specific marker low-grade fibromyxoid sarcoma. Am J Surg Pathol. 2011 May;35(5):733-41. doi: 10.1097/PAS.0b013e318210c268.
- Mohamed M, Fisher C, Thway K. Low-grade fibromyxoid sarcoma: Clinical, morphologic and genetic features. Ann Diagn Pathol. 2017 Jun;28:60-67. doi: 10.1016/j.anndiagpath.2017.04.001. Epub 2017 Apr 5.
- Mawas AS, Amatya VJ, Kushitani K, et al. MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung. Sci Rep. 2018 Jan 9;8(1):134. doi: 10.1038/s41598-017-18545-x.PMID: 29317712