Abstract：
CIC-rearranged sarcoma (CRS) is a group of high-grade undifferentiated small round cell sarcomas examined as a separate entity in the current WHO classification; since it shows more aggressive clinical behavior and distinct morphological and molecular features compared to Ewing sarcoma (ES). As CCNE1 expression is associated with tumor growth in CIC::DUX4 sarcomas, we aimed to demonstrate the value of cyclin E1 expression in CRS. Cyclin E1 immunohistochemistry and break-apart FISH for EWSR1 and CIC gene rearrangements were performed on 3-mm tissue microarrays composed of 40 small round cell tumors. Five cases were classified as CRS, whereas 22 were ES and 13 were unclassified (EWSR1-/CIC-). Among all three diagnostic groups, we found cyclin E1 expression level to be higher in CRS (80 %) and unclassified groups (61.5 %) compared to ES (4.5 %, p < 0.001). In addition, high cyclin E1 expression levels were associated with higher mean age at diagnosis, presence of atypical histology and myxoid stroma, low CD99 expression, and presence of metastasis at diagnosis. The sensitivity and specificity of high cyclin E1 expression in detecting non-ES cases were 95.5 % and 66.7 %, respectively. However, the correlation between cyclin E1 expression level and survival was not statistically significant. This is the first study that shows cyclin E1 immunohistochemical expression in EWSR1-negative undifferentiated small cell sarcomas, particularly CRS.
摘要：
CIC重排肉瘤（CRS）是一组高级未分化的小圆细胞肉瘤，在当前的WHO分类中被视为单独的实体；因为与尤文肉瘤（ES）相比，它显示出更具侵略性的临床行为和独特的形态和分子特征。由于CCNE1表达与CIC::DUX4肉瘤的肿瘤生长相关，我们旨在证明cyclinE1在CRS中表达的价值。在由40个小圆细胞肿瘤组成的3毫米组织微阵列上进行了CyclinE1免疫组织化学和EWSR1和CIC基因重排的分裂FISH。五例被归类为CRS，而22人ES和13人未分类（EWSR1-/CIC-）。在所有三个诊断组中，我们发现cyclinE1表达水平在CRS（80％）和未分类组（61.5％）高于ES（4.5％，p<0.001)。此外,高细胞周期蛋白E1表达水平与较高的诊断平均年龄相关，非典型组织学和粘液样基质的存在，低CD99表达，以及诊断时存在转移。细胞周期蛋白E1高表达检测非ES病例的敏感性和特异性分别为95.5%和66.7%,分别。然而,cyclinE1表达水平与生存率之间的相关性无统计学意义。这是第一个研究显示细胞周期蛋白E1在EWSR1阴性未分化小细胞肉瘤中的免疫组织化学表达，尤其是CRS。
