A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: A pathologic and molecular study of 18 cases Journal Article
| Authors: | Prieto Granada, C.; Zhang, L.; Chen, H. W.; Sung, Y. S.; Agaram, N. P.; Jungbluth, A. A.; Antonescu, C. R. |
| Article 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. |
| Keywords: | immunohistochemistry; adult; clinical article; middle aged; young adult; follow up; genetic analysis; reverse transcription polymerase chain reaction; gene expression; tumor volume; cytogenetics; pathology; immunoreactivity; cancer mortality; sarcoma; lung metastasis; fluorescence in situ hybridization; gene rearrangement; fibrosarcoma; gene fusion; cytoplasm; spindle cell; mitosis rate; epithelioid cell; rna sequence; mucin 4; fus gene; creb3l2 gene; low grade fibromyxoid sarcoma; genetic difference; human; male; female; priority journal; article; sclerosing epithelioid fibrosarcoma; ewsri gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 54 |
| Issue: | 1 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2015-01-01 |
| Start Page: | 28 |
| End Page: | 38 |
| Language: | English |
| DOI: | 10.1002/gcc.22215 |
| PROVIDER: | scopus |
| PMCID: | PMC4232448 |
| PUBMED: | 25231134 |
| DOI/URL: | |
| Notes: | Export Date: 2 March 2015 -- Source: Scopus |
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