MUC4 Is a Highly Sensitive and Specific Marker for Low-Grade Fibromyxoid Sarcoma.
Leona A Doyle, Emely Moller, Fredrik Mertens, Jason L Hornick. Brigham and Women's Hospital, Boston, MA; Lund University Hospital, Lund, Sweden
Background: Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive fibroblastic neoplasm characterized by alternating collagenous and myxoid areas, deceptively bland spindle cell morphology, a whorling architecture, and a t(7;16) translocation involving FUS and CREB3L2. Owing to variable morphology and a lack of discriminatory markers, LGFMS can be difficult to distinguish from benign mesenchymal tumors and other low grade sarcomas. Global gene expression profiling has identified differential expression of the mucin 4 (MUC4) gene in LGFMS compared to histologically similar tumors. MUC4 is a transmembrane glycoprotein that functions in cell growth signaling pathways; aberrant MUC4 expression has been reported in various carcinomas. We investigated MUC4 protein expression by immunohistochemistry (IHC) in a well-characterized series of LGFMS and other soft tissue tumors to determine the potential diagnostic utility of this novel marker.
Design: Whole tissue sections of 286 tumors were evaluated: 44 LGFMS (all with FUS rearrangement confirmed by FISH), 40 soft tissue perineuriomas, 22 myxofibrosarcomas (12 low, 6 intermediate, 4 high grade), 20 cellular myxomas, 20 solitary fibrous tumors, 20 low-grade malignant peripheral nerve sheath tumors, 20 desmoid fibromatosis, 20 neurofibromas, 20 schwannomas, 20 monophasic synovial sarcomas [all confirmed to harbor t(X;18)], 20 dermatofibrosarcoma protuberans, 10 myxoid liposarcomas, and 10 extraskeletal myxoid chondrosarcomas. IHC was performed following pressure cooker antigen retrieval using a mouse anti-MUC4 monoclonal antibody (1:500; 8G7; Santa Cruz). The extent of immunoreactivity was graded according to the percentage of positive tumor cells (0, no staining; 1+, <5%; 2+, 5-25%; 3+, 26-50%; 4+, 51-75%; and 5+, 76-100%).
Results: The LGFMS cases included 6 with marked hypercellularity, 4 with prominent HPC-like vessels, 3 with giant collagen rosettes, 3 with epithelioid morphology, 2 with focal nuclear pleomorphism, and 2 with areas of sclerosing epithelioid fibrosarcoma. All 44 LGFMS cases (100%) showed cytoplasmic staining for MUC4, which was usually diffuse and intense (5+ in 42 cases; 4+ in 1; 3+ in 1). All other tumor types were negative for MUC4, apart from focal reactivity in 6 (30%) monophasic synovial sarcomas and 1 (2%) soft tissue perineurioma.
Conclusions: MUC4 is a highly sensitive and specific IHC marker for LGFMS and can be helpful to distinguish this tumor type from histologic mimics. Expression of MUC4 in other soft tissue tumors is very limited in distribution.
Category: Bone & Soft Tissue
Monday, February 28, 2011 8:15 AM
Platform Session: Section F, Monday Morning