DDIT3 Immunohistochemistry Is a Useful Tool for the Diagnosis of Myxoid Liposarcoma.
DDIT3 Immunohistochemistry Is a Useful Tool for the Diagnosis of Myxoid Liposarcoma.
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DOI：
10.1097/pas.0000000000001564
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发表时间：
2021-02-01
期刊：
影响因子：
--
通讯作者：
Charville GW
中科院分区：
文献类型：
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作者：
Scapa JV;Cloutier JM;Raghavan SS;Peters-Schulze G;Varma S;Charville GW
粘液样脂肪肉瘤是一种恶性脂肪源性肿瘤，其特征是突出的树枝状毛细血管，偶见成脂肪细胞，粘液样背景中连续出现梭形细胞。粘液样脂肪肉瘤的复发性易位导致一种癌蛋白，由全长DDIT 3（CHOP）融合到FUS（TLS）或EWSR 1（较少）的N端片段组成。在此，我们利用识别N端区域表位的鼠单克隆抗体，探讨DDIT 3在粘液样脂肪肉瘤中表达的诊断意义。共研究300例肿瘤，我们发现在所有46例粘液样脂肪肉瘤中，有36例独特的肿瘤，包括6例高级别（圆形细胞）形态的弥漫性，中度至强烈的核定位抗DDIT 3免疫反应。DDIT 3免疫组化还强调了7例新辅助放疗治疗的粘液样脂肪肉瘤中独特的血管中心性生长模式。相反，绝大多数其他检查的脂肪瘤和粘液样肿瘤没有DDIT 3表达;在去分化脂肪肉瘤（6/39，15%）、孤立性纤维瘤（3/12，25%）、多形性脂肪肉瘤（1/15，7%）和高级别粘液纤维肉瘤（2/17，12%）中很少观察到少于10%的细胞中的有限的弱免疫反应性。虽然这种最小的DDIT 3表达与去分化脂肪肉瘤中DDIT 3扩增或粘液样脂肪肉瘤样形态无关，但有证据表明肉瘤（不包括粘液样脂肪肉瘤）的表达与暴露于新辅助放疗或细胞毒性化疗之间存在相关性。结果表明，DDIT 3免疫组化在粘液样和脂肪瘤性肿瘤的评价中可能具有实用性，以支持粘液样脂肪肉瘤的诊断。
Myxoid liposarcoma is a malignant adipogenic neoplasm characterized by prominent arborizing capillaries, occasional lipoblasts, and primitive-appearing spindle cells in a myxoid background. A recurrent translocation in myxoid liposarcoma results in an oncoprotein consisting of full-length DDIT3 (CHOP) fused to an N-terminal segment of either FUS (TLS) or, less often, EWSR1. Here, we explore the diagnostic significance of DDIT3 expression in myxoid liposarcoma using a mouse monoclonal antibody recognizing an epitope in the N-terminal region. Studying a total of 300 tumors, we find diffuse, moderate-to-strong nuclear-localized anti-DDIT3 immunoreactivity in all 46 cases of myxoid liposarcoma representing 36 unique tumors, including 6 cases with high-grade (round cell) morphology. DDIT3 immunohistochemistry also highlighted a distinctive vasculocentric growth pattern in 7 myxoid liposarcomas treated with neoadjuvant radiation. In contrast, the vast majority of other examined lipomatous and myxoid neoplasms exhibited no DDIT3 expression; limited, weak immunoreactivity in less than 10% of cells was infrequently observed in dedifferentiated liposarcoma (6/39, 15%), solitary fibrous tumor (3/12, 25%), pleomorphic liposarcoma (1/15, 7%), and high-grade myxofibrosarcoma (2/17, 12%). Although this minimal DDIT3 expression did not correlate with DDIT3 amplification or myxoid liposarcoma-like morphology in dedifferentiated liposarcoma, there was evidence among sarcomas (excluding myxoid liposarcoma) of a relationship between expression and exposure to neoadjuvant radiation or cytotoxic chemotherapy. The constellation of findings indicates that DDIT3 immunohistochemistry may have utility in the evaluation of myxoid and lipomatous neoplasms to support the diagnosis of myxoid liposarcoma.