Abstract:
ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.
摘要:
ISLET-1(ISL1)是LIM同源结构域转录因子。选择性ISL1表达显示在神经内分泌,非神经内分泌,和一些软组织肿瘤,包括促纤维增生性小圆细胞瘤(DSRCT)。我们评估了ISL1(克隆EP283,1:500,细胞标记)在288个软组织肿瘤中的特异性,其中包括17个DSRCT和其他组织学模拟。ISL1的阳性染色阈值设定为中等强度的>10%的肿瘤细胞核。ISLlIHC在15/16(94%)DSRCT中呈阳性,其中75%显示弥漫性(>50%)表达。ISL1在1/10(10%)尤因肉瘤(EWS)中呈阳性,7/13(54%)肺泡横纹肌肉瘤(RMS),14/22(63%)胚胎RMS,7/14(50%)滑膜肉瘤,15/16(93%)神经母细胞瘤,1/5(20%)肾母细胞瘤,2/4(50%)嗅觉神经母细胞瘤,和所有9个默克尔细胞癌。其他肿瘤,包括allCIC::DUX4肉瘤,除3/27平滑肌肉瘤外,均为阴性,各1个血管肉瘤,粘液样脂肪肉瘤,炎性肌纤维母细胞瘤,恶性周围神经鞘瘤,腱鞘巨细胞瘤,去分化LPS,和1个外胚膜瘤。总之,在测试的软组织肿瘤中,ISL1是DSRCT的高度敏感但中等特异性的标记,可用于区分圆形细胞模拟物,包括EWS和CIC::DUX4肉瘤。ISL1在这些肿瘤中的致癌作用值得进一步研究。