Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Digestive and General Surgery, Graduate School of Medicine, University of Ryukyus, Okinawa 903-0215, Japan.
Hum Pathol. 2019 Mar;85:162-167. doi: 10.1016/j.humpath.2018.11.004. Epub 2018 Nov 20.
The RNA-binding protein HuC/D displays a neuron-specific expression and is involved in neuronal differentiation and the maintenance of the nervous system. Here we investigated the diagnostic value of HuC/D in neuroblastomas. We evaluated 85 neuroblastic tumors: 81 neuroblastomas; 3 ganglioneuroblastomas, intermixed; 1 ganglioneuroma, maturing; and 101 other tumors consisting of 34 Ewing sarcomas, 14 nephroblastomas, 11 rhabdomyosarcomas, 15 pulmonary small cell carcinomas, 18 pancreatic neuroendocrine tumors, and 9 pheochromocytomas. Immunohistochemistry for HuC/D, PHOX2B, and tyrosine hydroxylase was performed. The immunoreactivity for HuC/D was semiquantified using the total score (TS; range, 0-8). HuC/D positivity was defined as a TS ≥6. The TS of the neuroblastic tumors (mean TS, 7.94) was significantly higher than those of the other small round cell tumors and neuroendocrine tumors (P < .001) except for the pheochromocytomas (mean TS, 6.89; P = .074). HuC/D was positive in all 85 neuroblastic tumors, 1 (2.9%) Ewing sarcoma, 1 (6.7%) pulmonary small cell carcinoma, and 8 (89%) pheochromocytomas. PHOX2B was positive in all of the neuroblastic tumors and pheochromocytomas. Tyrosine hydroxylase was positive in 80 (94%) neuroblastic tumors, 1 (9.1%) rhabdomyosarcoma, and all of the pheochromocytomas. Therefore, HuC/D serves as a highly sensitive diagnostic marker to distinguish neuroblastomas from other small round cell tumors. The combination of HuC/D and PHOX2B staining may be valuable for the diagnosis of neuroblastic tumors, especially in the assessment of small sections. HuC/D expression in tumors may be related to catecholamine production or a neural crest-derived cell origin.
RNA 结合蛋白 HuC/D 表现出神经元特异性表达，参与神经元分化和神经系统的维持。在这里，我们研究了 HuC/D 在神经母细胞瘤中的诊断价值。我们评估了 85 例神经母细胞瘤：81 例神经母细胞瘤；3 例混合性神经节母细胞瘤；1 例成熟性神经节细胞瘤；101 例其他肿瘤，包括 34 例尤文肉瘤、14 例肾母细胞瘤、11 例横纹肌肉瘤、15 例肺小细胞癌、18 例胰腺神经内分泌肿瘤和 9 例嗜铬细胞瘤。进行 HuC/D、PHOX2B 和酪氨酸羟化酶的免疫组织化学染色。使用总评分（TS；范围 0-8）对 HuC/D 的免疫反应性进行半定量评估。将 HuC/D 阳性定义为 TS≥6。神经母细胞瘤的 TS（平均 TS 为 7.94）明显高于其他小圆细胞肿瘤和神经内分泌肿瘤（P＜0.001），除了嗜铬细胞瘤（平均 TS 为 6.89；P=0.074）。所有 85 例神经母细胞瘤、1 例（2.9%）尤文肉瘤、1 例（6.7%）肺小细胞癌和 8 例（89%）嗜铬细胞瘤均为 HuC/D 阳性。所有神经母细胞瘤和嗜铬细胞瘤均为 PHOX2B 阳性。80 例（94%）神经母细胞瘤、1 例（9.1%）横纹肌肉瘤和所有嗜铬细胞瘤均为酪氨酸羟化酶阳性。因此，HuC/D 可作为一种高度敏感的诊断标志物，用于区分神经母细胞瘤与其他小圆细胞肿瘤。HuC/D 和 PHOX2B 染色的组合对于神经母细胞瘤的诊断可能具有重要价值，尤其是在评估小切片时。肿瘤中 HuC/D 的表达可能与儿茶酚胺的产生或神经嵴衍生细胞起源有关。
