MUC4 Is a Sensitive and Specific Marker for Sclerosing Epithelioid Fibrosarcoma: Association with FUS Gene Rearrangement
Leona A Doyle, Wei-Lien Wang, Paola Dal Cin, Alexander J Lazar, Christopher DM Fletcher, Jason L Hornick. Brigham and Women's Hospital & Harvard Medical School, Boston, MA; The University of Texas M.D. Anderson Cancer Center, Houston, TX
Background: Sclerosing epithelioid fibrosarcoma (SEF) is a rare aggressive fibroblastic neoplasm composed of cords of epithelioid cells embedded in a dense collagenous stroma. The reported immunophenotype of SEF is non-specific. Some SEF cases show morphologic and molecular overlap with low-grade fibromyxoid sarcoma (LGFMS), suggesting a relationship between these tumor types. MUC4 has recently been identified as a sensitive and specific marker for LGFMS; MUC4 expression was also observed in 2 tumors with hybrid features of SEF and LGFMS. We investigated MUC4 expression in SEF and other epithelioid soft tissue tumors to determine (1) the potential diagnostic utility of MUC4 for SEF and (2) the association between MUC4 expression and FUS rearrangement in SEF.
Design: Whole sections of 146 tumors were evaluated: 34 SEF cases (8 hybrid LGFMS/SEF), 20 epithelioid sarcoma, 11 clear cell sarcoma, 11 metastatic melanoma, 10 PEComa, 10 alveolar soft part sarcoma, 10 epithelioid angiosarcoma, 10 epithelioid hemangioendothelioma, 10 epithelioid gastrointestinal stromal tumor (GIST), 10 myoepithelial carcinoma (MEC), and 10 biphasic synovial sarcoma (B-SYS). Immunohistochemistry was performed following antigen retrieval using a mouse anti-MUC4 monoclonal antibody (1:500; 8G7; Santa Cruz). FISH was performed on 33 SEF cases using FUS break-apart probes (Abbott).
Results: Strong diffuse cytoplasmic staining for MUC4 was observed in 25 of 34 (74%) SEF cases, including all 8 hybrid tumors. FUS rearrangement was found in 7 of 20 (35%) MUC4-positive SEF cases with successful FISH. The prevalence of FUS rearrangement was similar in hybrid LGFMS/SEF and SEF cases without an LGFMS component. FUS rearrangement was not detected in any MUC4-negative SEF cases. MUC4 expression was also seen in 9 of 10 (90%) B-SYS cases, predominantly in the glandular component. All other tumor types were negative for MUC4, apart from focal reactivity in 2 epithelioid GISTs and 1 MEC.
Conclusions: MUC4 is a sensitive and relatively specific marker for SEF. MUC4 expression correlates with glandular epithelial differentiation in B-SYS and is very limited in other epithelioid soft tissue tumors. These findings suggest that SEF are biologically heterogeneous. MUC4-positive SEF with FUS rearrangement are likely closely related to LGFMS. MUC4-positive SEF that lack FUS rearrangement may be related to LGFMS but could have alternate gene fusions. SEF without MUC4 expression probably represent a distinct group of tumors.
Category: Bone & Soft Tissue
Tuesday, March 20, 2012 9:00 AM
Platform Session: Section G, Tuesday Morning