Muc-4 Expression and FUS Rearrangement in Sclerosing Epithelioid Fibrosarcomas: A Pathological Study of 20 Cases Further Supporting Relationship with Low Grade Fibromyxoid Sarcoma
Florian Puls, Khin Thway, Angela Niblett, Florian Laenger, Vaiyapuri Sumathi, Cyril Fisher, Chas C Mangham, Lars-Gunnar Kindblom. Royal Orthopaedic Hospital, Birmingham, United Kingdom; Royal Marsden Hospital, London, United Kingdom; Medical School Hannover, Hannover, Germany; Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry, United Kingdom
Background: Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive sarcoma with a predilection for the deep soft tissues of the extremities and trunk and a propensity for local recurrence, metastasis and tumor-related death. A subset of SEF shows morphologic and molecular overlap with low grade fibromyxoid sarcomas (LGFMS). LGFMS characteristically harbors FUS-CREB3L1/L2 and has recently been shown to express Muc-4, which can be used as a diagnostic immunohistochemical marker. We have studied MUC-4 expression and evidence of FUS rearrangement in a large series of SEF. Pathological findings and clinical outcome were compared to a cohort of 14 “classic” LGFMS.
Design: 20 cases of SEF and 14 LGFMS were retrieved, reviewed and stained for Muc-4. RT-PCR and/or FISH for FUS-break apart were performed. Clinical follow up was obtained.
Results: 14/20 SEF and 14/14 LGFMS showed Muc-4 expression; FUS-rearrangement was detected in 2/9 SEF (both Muc-4 positive) and 8/8 LGMFS tested. Clinical follow up was obtained from 19 SEF cases (4 to 216, median 31 months) and 13 LGFMS (2 to 121, median 37 months). Metastastic disease occurred in 14/19 SEF patients (metastasis-free survival 0 to 120, median 12 months) and 6 patients died of tumor (survival 4 to 73, median 31.5 months). There was no significant difference between Muc-4 positive and Muc-4 negative SEF with regard to metastasis and overall survival. Of 13 LGFMS cases, 3 had metastasized (2 at presentation, one after 53 months), all alive 2, 7 and 121 months after diagnosis. Metastasis-free survival and overall survival of Muc-4 positive SEF were significantly shorter when compared to LGFMS.
Conclusions: A high proportion of SEF expresses Muc-4 and a smaller proportion shows FUS rearrangement. The findings support a histogenic relationship between LGFMS and SEF. The fact that SEF shows a more aggressive biological behavior in respect to metastatic potential and survival justifies the continuous distinction between the entities.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 15, Monday Afternoon