*Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden †Department of Musculoskeletal Pathology and Orthopaedic Oncology, Royal Orthopaedic Hospital NHS Foundation Trust and Division of Cancer Studies, Medical School, University of Birmingham, Birmingham ‡Department of Histopathology, Royal Marsden Hospital, London, UK.
Am J Surg Pathol. 2014 Jun;38(6):801-8. doi: 10.1097/PAS.0000000000000158.
Sclerosing epithelioid fibrosarcoma (SEF) and low-grade fibromyxoid sarcoma (LGFMS) are 2 distinct types of sarcoma, with a subset of cases showing overlapping morphologic and immunohistochemical features. LGFMS is characterized by expression of the MUC4 protein, and about 90% of cases display a distinctive FUS-CREB3L2 gene fusion. In addition, SEF is often MUC4 positive, but is genetically less well studied. Fluorescence in situ hybridization (FISH) studies have shown involvement of the FUS gene in the majority of so-called hybrid LGFMS/SEF and in 10% to 25% of sarcomas with pure SEF morphology. In this study, we investigated a series of 10 primary tumors showing pure SEF morphology, 4 cases of LGFMS that at local or distant relapse showed predominant SEF morphology, and 1 primary hybrid LGFMS/SEF. All but 1 case showed diffuse expression for MUC4. Using FISH, reverse transcription polymerase chain reaction, and/or mRNA sequencing in selected cases, we found recurrent EWSR1-CREB3L1 fusion transcripts by reverse transcription polymerase chain reaction in 3/10 pure SEF cases and splits and deletions of the EWSR1 and/or CREB3L1 genes by FISH in 6 additional cases. All 5 cases of LGFMS with progression to SEF morphology or hybrid features had FUS-CREB3L2 fusion transcripts. Our results indicate that EWSR1 and CREB3L1 rearrangements are predominant over FUS and CREB3L2 rearrangements in pure SEF, highlighting that SEF and LGFMS are different tumor types, with different impacts on patient outcome.
硬化性上皮样纤维肉瘤（SEF）和低度恶性纤维黏液样肉瘤（LGFMS）是两种不同类型的肉瘤，其中一部分病例具有重叠的形态学和免疫组织化学特征。LGFMS 的特征是表达 MUC4 蛋白，约 90%的病例显示出独特的 FUS-CREB3L2 基因融合。此外，SEF 通常 MUC4 阳性，但在遗传学上研究较少。荧光原位杂交（FISH）研究表明，大多数所谓的混合 LGFMS/SEF 以及 10%至 25%具有纯 SEF 形态的肉瘤中，FUS 基因都存在参与。在这项研究中，我们研究了 10 例表现出纯 SEF 形态的原发性肿瘤，4 例局部或远处复发时表现出主要 SEF 形态的 LGFMS，以及 1 例原发性混合 LGFMS/SEF。除了 1 例，所有病例均表现为 MUC4 的弥漫性表达。在选定的病例中使用 FISH、逆转录聚合酶链反应和/或 mRNA 测序，我们发现 3/10 例纯 SEF 病例通过逆转录聚合酶链反应检测到 EWSR1-CREB3L1 融合转录本，另外 6 例病例通过 FISH 检测到 EWSR1 和/或 CREB3L1 基因的分裂和缺失。所有 5 例进展为 SEF 形态或混合特征的 LGFMS 均具有 FUS-CREB3L2 融合转录本。我们的结果表明，在纯 SEF 中，EWSR1 和 CREB3L1 重排比 FUS 和 CREB3L2 重排更为常见，这突出表明 SEF 和 LGFMS 是两种不同的肿瘤类型，对患者预后的影响也不同。
