HuC/D expression in small round cell tumors and neuroendocrine tumors: a useful tool for distinguishing neuroblastoma from childhood small round cell tumors

Abstract

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 b .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.

Anaplastic Lymphoma Kinase Overexpression Is Associated with Aggressive Phenotypic Characteristics of Ovarian High-Grade Serous Carcinoma

“…Hierarchical clustering revealed that the genes could be readily categorized into 14 groups (Figure 5A). The study focused on the ELAVL3/HuC gene, which is an RNA-binding protein that displays a neuron-specific expression, 41,42 because the molecule was overexpressed by z50-fold in group XII. In addition, ALK overexpression is significantly associated with several general neuronal markers, including N-myc and Sox11, in uterine carcinosarcoma.…”

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

“…ELAVL4 (HuD) had the most significant differential expression of its family (p = 1.6 × 10 −26 ). ELAVL2-4 are necessary and sufficient to induce neuronal differentiation [69], and are potential diagnostic markers of neuroblastoma (distinguishing neuroblastoma from similar tumours) [70]. They promote the stabilisation and/or translation of transcripts containing AU-rich elements (ARE), and Lazarova and colleagues found that ELAVL4 binds to the 3´UTR of the MYCN mRNA, stabilising it [71].…”

Adrenal ganglioneuroma: Prognostic factors (Review)

“…However, when it comes to neuroblastoma, an aggressive neural crest-derived tumor with an overall survival rate of less than 50%, several abnormal signal transduction pathways have been identified including: TP53, ALT, ADAM22, ATRX, GAL, RAS/MAPK, KLHL13, β3-adrenergic receptor, and TWIST1 (58,59). HuC/D, an RNA binding protein, may be a marker of neuroblastic cells but not a distinctive factor between neuroblastoma/ganglioneuroma (60). Tyrosine hydroxylase (TH) has been used as a sympathoadrenal marker for tumors originating from the neural crest, and currently Phox2B has been confirmed to be a better marker especially for undifferentiated neuroblastoma and cases with negative TH expression (61).…”