ETV4 is a useful marker for the diagnosis of CIC-rearranged undifferentiated round-cell sarcomas: a study of 127 cases including mimicking lesions
ETV4 is a useful marker for the diagnosis of CIC-rearranged undifferentiated round-cell sarcomas: a study of 127 cases including mimicking lesions
复制标题
DOI：
10.1038/modpathol.2016.155
复制
发表时间：
2016-12-01
期刊：
影响因子：
7.5
通讯作者：
Coindre, Jean-Michel
中科院分区：
文献类型：
--
作者：
Le Guellec, Sophie;Velasco, Valerie;Coindre, Jean-Michel
原始圆细胞肉瘤的亚群仍然难以诊断和分类。其中有一种罕见的圆形细胞肉瘤，具有CIC基因重排，称为C/C重排未分化圆形细胞肉瘤，最常见的是与DUX 4基因融合。由于其侵略性的临床行为和潜在的治疗意义，准确识别这种新的软组织肉瘤是必要的。确诊需要分子确认，但只有少数中心能够进行这种测试。一些研究表明PEA 3亚家族基因，特别是ETV 4（属于ETS转录因子家族），在C/C重排未分化的圆细胞肉瘤中上调。我们进行了详细的免疫组化分析，以调查ETV 4在CIC重排的未分化的圆细胞肉瘤及其潜在的模拟（特别是尤文肉瘤）的表达。研究队列包括17例CIC重排未分化圆细胞肉瘤和110例形态学类似CIC重排未分化圆细胞肉瘤的肿瘤：43例尤文肉瘤，25例肺泡横纹肌肉瘤，20例低分化圆细胞滑膜肉瘤，10例促结缔组织增生性圆细胞肿瘤，5例BCOR-CCNB 3肉瘤，5例淋巴母细胞淋巴瘤和2例横纹肌样肿瘤。所有CIC重排的未分化圆细胞肉瘤（空芯针穿刺活检和开放活检）均为ETV 4阳性，具有强弥漫性核模式。在其他110例肿瘤中，只有6例（4例尤文肉瘤，1例腺泡状横纹肌肉瘤和1例促结缔组织增生性圆细胞瘤）显示局灶性（< 5%的肿瘤细胞）和非常弱的ETV 4核表达;所有其他肿瘤均为ETV 4完全阴性。我们的结论是，系统的免疫组化分析ETV 4可以诊断未分化的圆细胞肉瘤（没有肉瘤相关易位的分子标志物），如CIC重排的未分化的圆细胞肉瘤。
Subsets of primitive round-cell sarcomas remain difficult to diagnose and classify. Among these is a rare round cell sarcoma that harbors a CIC gene rearrangement known as C/C-rearranged undifferentiated round-cell sarcoma, which is most commonly fused to the DUX4 gene. Owing to its aggressive clinical behavior and potential therapeutic implications, accurate identification of this novel soft tissue sarcoma is necessary. Definitive diagnosis requires molecular confirmation, but only a few centers are as yet able to perform this test. Several studies have shown that PEA3 subfamily genes, notably ETV4 (belonging to the family of ETS transcription factors), are upregulated in C/C-rearranged undifferentiated round-cell sarcomas. We performed a detailed immunohistochemical analysis to investigate ETV4 expression in CIC-rearranged undifferentiated round-cell sarcomas and their potential mimics (especially Ewing sarcomas). The study cohort included 17 cases of CIC-rearranged undifferentiated round-cell sarcomas, and 110 tumors that morphologically mimic CIC-rearranged undifferentiated round-cell sarcomas: 43 Ewing sarcomas, 25 alveolar rhabdomyosarcomas, 20 poorly differentiated round-cell synovial sarcomas, 10 desmoplastic round-cell tumors, 5 BCOR-CCNB3 sarcomas, 5 lymphoblastic lymphomas, and 2 rhabdoid tumors. All CIC-rearranged undifferentiated round-cell sarcomas (on core needle biopsies and open biopsies) were ETV4-positive with a strong diffuse nuclear pattern. Among the other 110 tumors, only six cases (four Ewing sarcomas, one alveolar rhabdomyosarcoma, and one desmoplastic round-cell tumor) showed focal (< 5% of tumor cells) and very weak nuclear expression of ETV4; all other tumors were completely negative for ETV4. We conclude that systematic immunohistochemical analysis of ETV4 makes it possible to diagnose undifferentiated round-cell sarcomas (with no molecular markers for sarcoma-associated translocation) such as CIC-rearranged undifferentiated round-cell sarcoma.