Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall.
Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall.
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ERG 和 CD31 在 CIC 重排肉瘤子集中的共表达：潜在的诊断陷阱。
DOI：
10.1038/s41379-022-01078-8
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发表时间：
2022
期刊：
影响因子：
7.5
通讯作者：
Yoshida Akihiko.
中科院分区：
文献类型：
--
作者：
Kojima Naoki;Arai Yasuhito;Satomi Kaishi;Kubo Takashi;Matsushita Yuko;Mori Taisuke;Matsushita Hiromichi;Ushijima Toshikazu;Yatabe Yasushi;Shibata Tatsuhiro;Yonemori Kan;Ichimura Koichi;Ichikawa Hitoshi;Kawai Akira;Yoshida Akihiko.
CIC重排肉瘤的特点是圆形细胞未分化，ETV4和WT1的表达频繁，并有侵袭性行为。一例CIC-DUX4融合和ERG/CD31共表达的病例促使我们系统地研究了30例CIC重排肉瘤的ERG和CD31的表达状况。其中半数(15例)ERG在5~100%的肿瘤细胞中呈中强表达，其中9例呈异质性膜性CD31反应，其中4例呈弥漫或强表达。无一例ERG/CD31呈均匀强阳性和弥漫性共表达，但有3例初步诊断为血管肉瘤，治疗无反应。9例ERG+/CD31+CIC重排肉瘤的临床病理特征与其余21例无明显差异。5例显示局灶性出血性裂隙/囊肿，似血管间隙。所有肿瘤均表达ETV4和/或核WT1，7例证实融合为DUX4。经下一代测序检查的四种肿瘤含有noCIC错义突变。1例CD31+CIC重排肉瘤与CD31−CIC重排肉瘤聚在一起，但与血管肉瘤相距较远。与缺乏CIC重排的上皮样血管肉瘤相比，ERG+/CD31+CIC重排肉瘤的特点是局部粘液样改变和完全缺乏血管形成结构。血管肉瘤ERG和CD31均呈强阳性表达，但无ETV4或核WT1阳性表达。在CIC重排的肉瘤中，ERG/CD31的异质性共表达是血管肉瘤的一个临床相关陷阱，因为这两种疾病的治疗方式不同。
CIC-rearranged sarcoma is characterized by round cell undifferentiated histology, frequent expression of ETV4 and WT1, and aggressive behavior. A clinical encounter of a case withCIC-DUX4fusion and ERG/CD31 co-expression prompted us to systematically investigate ERG and CD31 expression status in 30 archival cases ofCIC-rearranged sarcoma. Half (15) of them showed moderate or strong ERG expression in <5–100% of tumor cells, among which nine showed heterogeneous membranous CD31 reactivity, including four cases each showing diffuse or strong expression. None of them showed uniformly strong and diffuse ERG/CD31 co-expression; however, three cases were initially interpreted and treated as angiosarcoma without response. Except for smaller superficial tumor enrichment, the clinicopathological characteristics of these nine cases of ERG+/CD31+CIC-rearranged sarcoma did not differ from those of remaining 21 cases. Five showed focal hemorrhagic clefts/cysts, mimicking vascular spaces. All tumors expressed ETV4 and/or nuclear WT1, and fusion toDUX4was confirmed in seven cases. Four tumors examined by next-generation sequencing harbored noCICmissense mutations. Using DNA methylation profiling, one CD31+CIC-rearranged sarcoma was clustered with CD31−CIC-rearranged sarcomas, but distant from angiosarcomas. When compared with epithelioid angiosarcomas lackingCICrearrangements, ERG+/CD31+CIC-rearranged sarcomas were distinguished by focal myxoid change and the entire lack of vasoformative architecture. The angiosarcomas were characterized by uniform strong expression of ERG and CD31, but none of them were found positive for ETV4 or nuclear WT1. Heterogeneous ERG/CD31 co-expression in a subset ofCIC-rearranged sarcoma is a clinically relevant pitfall for angiosarcoma, as these two diseases are treated differently.