Original contributionHuC/D expression in small round cell tumors and neuroendocrine tumors: a useful tool for distinguishing neuroblastoma from childhood small round cell tumors☆
Introduction
Neuroblastomas are small round cell tumors that arise mostly in the adrenal glands and sympathetic nervous system. They are the most common extracranial solid tumor in children. Spontaneous regression and maturation to a benign ganglioneuroma are the characteristic features of neuroblastomas [1], [2], [3], [4], [5], and it is also known that chemotherapy leads to the maturation of neuroblastoma cells. Neuroblastoma cells are typically positive for neural antibodies (eg, neuron-specific enolase, synaptophysin, chromogranin A, NB84, and S-100 protein) [6], [7], but these antibodies are not specific to neuroblastoma [8], [9]. Tyrosine hydroxylase (TH) was the most widely used sympathoadrenal marker specific for neuroblastoma, but its sensitivity was insufficient (84%) [10], [11]. The protein known as paired-like homeobox 2b (PHOX2B) has recently attracted attention as a sensitive and specific marker for neuroblastoma.
HuC/D, a member of the Hu family, is an RNA-binding protein that displays a neuron-specific expression and is involved in neuronal differentiation and the maintenance of the nervous system [12], [13]. It has also been reported that HuC/D is a credible pan-neuronal marker for the enteric nervous system neurons [14], [15]. However, there are few published studies about HuC/D expression in neuroblastoma.
We conducted the present study to determine the HuC/D expression along with PHOX2B and TH expressions in neuroblastomas, small round cell tumors, and neuroendocrine tumors, and we discuss the potential utility of HuC/D expression as a differential diagnostic tool in neuroblastoma.
Section snippets
Patients and tissue samples
This study was approved by the Ethics Committee of Kyushu University (no. 29-429). We examined 85 paraffin-embedded samples from neuroblastic tumor tissue registered in the Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, between 1996 and 2015. Clinicopathological data were obtained from the patients' medical charts. We also stained (as comparison samples) other small round cell tumors and neuroendocrine tumors, comprising 34 Ewing sarcomas, 14
Clinicopathological characteristics
The clinicopathological features of the patients with neuroblastic tumors and the comparative tumors are summarized in Tables 1 and 2. In the group of neuroblastic tumor cases, all 85 patients were children (median age, 0 years; range, 0-8 years).
HuC/D expression
The results of the immunohistochemical analysis are summarized in Table 3. In regard to extent of staining, 98% (83/85) of the neuroblastic tumors showed a PS value of 5 (Figure A). In these cases, the percentage of positive tumor cells was almost
Discussion
In this study, we evaluated the immunohistochemical HuC/D expression profile in neuroblastic tumors, small round cell tumors, and neuroendocrine tumors. The results showed that HuC/D was expressed more diffusely and strongly in the neuroblastic tumors than in the other tumors, with the exception of the pheochromocytomas.
It is of note that HuC/D was reported to be a useful pan-neuronal marker in both central and enteric nervous system neurons [12], [13], [14], [15]. Few studies have addressed
Supplementary data
The following are the supplementary data to this article.
Acknowledgments
The English language used in this article was revised by KN International (http://www.kninter.com/).
References (25)
- et al.
Why does stage 4s neuroblastoma regress spontaneously?
Lancet
(1994) Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumors
Ann Diagn Pathol
(2008)Diagnosis and classification of the small round-cell tumors of childhood
Am J Pathol
(1999)- et al.
Differentiation of ganglion cells and amacrine cells in the rat retina: correlation with expression of HuC/D and GAP-43 proteins
Brain Res Dev Brain Res
(2003) - et al.
Expression of mRNA for the elav-like neural-specific RNA binding protein, HuD, during nervous system development
Brain Res Dev Brain Res
(1998) - et al.
Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers
J Neurosci Methods
(2004) - et al.
Neuroblastoma
BMJ
(2017) Spontaneous regression of metastatic cancer: learning from neuroblastoma
Nat Rev Cancer
(2014)- et al.
Mechanisms of neuroblastoma regression
Nat Rev Clin Oncol
(2014) Neuroblastoma: biological insights into a clinical enigma
Nat Rev Cancer
(2003)
Expression of pan-neuroendocrine proteins in 53 neuroblastic tumors. An immunohistochemical study with neuron-specific enolase, chromogranin, and synaptophysin
Arch Pathol Lab Med
NB84: a new monoclonal antibody for the recognition of neuroblastoma in routinely processed material
J Pathol
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Competing interests: The authors declare that there are no conflicts of interest to disclose.