The Expression of Mucin-4 (MUC4) in Sarcomas Apart From Sclerosing Epithelioid Fibrosarcoma and Low-Grade Fibromyxoid Sarcoma

Abstract

Background Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are two rare but aggressive soft tissue sarcomas that can be difficult to distinguish due to histopathological similarities. The present study examines the diagnostic capacities of mucin-4 (MUC4), a transmembrane mucin, in identifying different types of sarcomas and broadens its evaluation to include a wide range of sarcomas. Methods Immunohistochemical (IHC) examination of tissue samples from various sarcomas was performed using a mouse anti-MUC4 monoclonal antibody. IHC was conducted on 4-mm thick formalin-fixed paraffin-embedded tissue sections after pressure cooker antigen retrieval with a mouse anti-MUC4 monoclonal antibody. Results MUC4 was shown to be highly expressed in SEF (n=13) and LGFMS (n=10), while focal positivity in synovial sarcoma (n=1). Other sarcomas, such as malignant peripheral nerve sheath tumors, fibrosarcoma, leiomyosarcoma, liposarcoma, and myxofibrosarcoma, exhibited no expression (n=0). These findings are consistent with previous research and support MUC4 specificity as a SEF and LGFMS marker. This study provides information on the diagnostic efficacy of MUC4, particularly in the context of certain subtypes. It not only helps our understanding of these unique instances, but it also provides context for histopathological and IHC findings in soft tissue sarcoma. Furthermore, this study investigates the influence of age and gender on MUC4 expression in a range of sarcomas, which was typically understudied in the literature and found no relation with expression of MUC4. Conclusion In conclusion, this study adds to our understanding of soft tissue sarcomas by emphasizing the crucial role of MUC4 in certain sarcoma subtypes while acknowledging the complex variety of the sarcoma landscape. Further research is needed to understand the molecular mechanism that governs marker expression patterns, as well as the therapeutic implications.

Keywords: lgfms; low-grade fibromyxoid sarcoma; muc4; sclerosing epithelioid fibrosarcoma; sef; synovial sarcoma.

Figure 1. Histopathological characteristics of fibrosarcoma involving the thigh; an infiltrative tumor composed of spindle cells with moderate to marked atypia (40x)

Figure 2. Fibrosarcoma involving thigh: No expression of MUC4 (40x)

MUC4: Mucin-4

Figure 3. Liposarcoma involving retroperitoneum, showing myxoid background composed of sheets of lipoblasts and giant cells (20x)

Figure 4. Liposarcoma of retroperitoneum showing positive expression for MDM2 (20x)

MDM2: Murine double minute 2

Figure 5. Liposarcoma of retroperitoneum showing positive expression for p16 (40x)

p16 (also known as p16^INK4a, cyclin-dependent kinase inhibitor 2A, CKN2A)

Figure 6. No expression of MUC4 in reteroperitoneal liposarcoma (40x)

MUC4: Mucin-4

Figure 7. Malignant peripheral nerve sheath tumor of the calf: an infiltrative tumor composed of spindle cells with pleomorphic nuclei arranged in whorling and diffuse patterns (40x)

Figure 8. No expression of MUC4 in MPNST of lower limb (calf) (40x)

MUC4: Mucin-4, MPNST: Malignant peripheral nerve sheath tumor

Figure 9. MPNST of the lower limb, showing positive expression of S-100 protein (40x)

MPNST: Malignant peripheral nerve sheath tumor S-100 protein (solubility in 100%-saturated solution with ammonium sulphate at neutral pH)

Figure 10. Myxofibrosarcoma involving chest wall: an infiltrative tumor arranged in a lobular configuration having fibromyxoid stroma and arcuate-like vascular pattern (40x)

Figure 11. No expression of MUC4 in myxofibrosarcoma of the chest wall (40x)

MUC4: Mucin-4

Figure 12. Synovial sarcoma of the forearm: an infiltrative tumor composed of spindle cells arranged in fascicles and background showing hemangiopericytoma-like vascular pattern (40x)

Figure 13. Upper limb synovial sarcoma showing strong positive expression of TLE1 (40x)

TLE1: Transducin-like enhancer protein 1

Figure 14. Upper limb synovial sarcoma showing focal positivity for MUC4 (40x)

MUC4: Mucin-4

Figure 15. Leiomyosarcoma of lower limb; fascicles of smooth muscle fibers displaying a moderate degree of nuclear atypia and pleomorphism (40x)

Figure 16. Leiomyosarcoma showing positive expression of desmin in smooth muscle fibers (40x)

Figure 17. Leiomyosarcoma: Positive expression for smooth muscle fibers for Caldesmon (10x)

Figure 18. Leiomyosarcoma: No expression of MUC4 in the smooth muscle fibers (10x)

MUC4: Mucin-4

Figure 19. Sclerosing epithelioid fibrosarcoma involving the trunk, composed of round to polygonal epithelioid cells with sparse cytoplasm, round-to-oval nuclei, and inconspicuous nucleoli (20x)

Figure 20. Low-grade fibromyxoid sarcoma: An infiltrative tumor of the upper limb showing moderately cellular bland-looking fusiform spindle cell with abrupt transition to myxoid areas (arrowhead) (40x)

Figure 21. Positive expression of MUC4 in SEF of the trunk (20x)

MUC4: Mucin-4, SEF: Sclerosing epithelioid fibrosarcoma

Figure 22. Strong positive expression of MUC4 in LGFMS (40x)

MUC4: Mucin-4, LGFMS: Low-grade fibromyxoid sarcoma