title: A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: a pathologic and molecular study of 18 cases.
abstract: Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue tumor exhibiting considerable morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Moreover, both SEF and LGFMS show MUC4 expression by immunohistochemistry. While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors. In contrast, recent studies pointed out that SEF harbor frequent EWSR1 rearrangements, with only a minority of cases showing FUS-CREB3L2 fusions. In an effort to further characterize the molecular characteristics of pure SEF and hybrid SEF/LGFMS lesions, we undertook a clinicopathologic, immunohistochemical and genetic analysis of a series of 10 SEF and 8 hybrid SEF/LGFMS tumors. The mortality rate was similar between the two groups, 44% within the pure SEF group and 37% in the hybrid SEF/LGFMS with a mean overall follow-up of 66 months. All but one pure SEF and all hybrid SEF/LGFMS-tested cases showed MUC4 immunoreactivity. The majority (90%) of pure SEF cases showed EWSR1 gene rearrangements by fluorescence in situ hybridization with only one case exhibiting FUS rearrangement. Of the nine EWSR1 positive cases, six cases harbored CREB3L1 break-apart, two had CREB3L2 rearrangement (a previously unreported finding) and one lacked evidence of CREB3L1/2 abnormalities. In contrast, all hybrid SEF/LGFMS tumors exhibited FUS and CREB3L2 rearrangements. These results further demarcate a relative cytogenetic dichotomy between pure SEF, often characterized by EWSR1 rearrangements, and hybrid SEF/LGFMS, harboring FUS-CREB3L2 fusion; the latter group recapitulating the genotype of LGFMS.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Carlos
authors.initials: C
authors.lastname: Prieto-Granada
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Yun-Shao
authors.initials: YS
authors.lastname: Sung
authors.forename: Narasimhan P
authors.initials: NP
authors.lastname: Agaram
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D055264:Mucin-4 / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012598:Sclerosis; D055815:Young Adult
chemical_list: C485618:CREB3L1 protein, human; D002148:Calmodulin-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C500986:EWSR1 protein, human; C524658:MUC4 protein, human; D055264:Mucin-4; D009419:Nerve Tissue Proteins; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins