Utility of Phox2b immunohistochemical stain in neural crest tumours and non‐neural crest tumours in paediatric patients

Warren, Mikako; Matsuno, Ryosuke; Tran, Henry; Shimada, Hiroyuki

doi:10.1111/his.13412

Cited by 27 publications

(20 citation statements)

References 19 publications

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“…The effects of PHOX2B mutations on neuroblastoma, their associations with other well‐described molecular alterations, with prognosis and potential therapeutic options, continue to be explored. The role of PHOX2B immunostain in the diagnosis of neuroblastoma has also been described recently in several studies with high specificity and sensitivity …”

Section: Discussionmentioning

confidence: 87%

“…Recently, several studies have looked at the utility of PHOX2B immunostain as a way to distinguish peripheral neuroblastic tumours from other small blue cell tumours, and it was demonstrated that PHOX2B has extensive nuclear expression in all neuroblastic and sympathetic nervous tumours, and it is negative in small blue cell tumours as Ewing sarcoma, desmoplastic small round blue cell tumour, hepatoblastoma and alveolar rhabdomyosarcoma . In one of these studies Hung et al .…”

Section: Introductionmentioning

confidence: 99%

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PHOX2B is a reliable immunomarker in distinguishing peripheral neuroblastic tumours from CNS embryonal tumours

et al. 2018

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

PHOX2B is a reliable immunomarker in distinguishing peripheral neuroblastic tumours from CNS embryonal tumours

et al. 2018

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“…IHC using anti-Phox2b antibody has been validated for clinical uses at our CLIA-certified laboratory as previously described. 10…”

Section: Methodsmentioning

confidence: 99%

“…Nuclear Phox2b expression was uniformly strong in undifferentiated, poorly differentiated, and differentiating neuroblastoma cells and became more variable in maturing and mature ganglion cells and pheochromocytoma/paraganglioma cells. 10…”

Section: Introductionmentioning

confidence: 99%

Phox2b Immunohistochemical Staining in Detecting Enteric Neural Crest Cells in Hirschsprung Disease

et al. 2020

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Background It can be challenging to recognize undifferentiated/immature ganglion cells, especially single forms. Ganglion cells and glia are derived from enteric neural crest cells (ENCCs), a group of autonomic nervous system (ANS)-lineage neural crest progenitors that PHOX2B regulates. Phox2b is an excellent marker for neoplastic and non-neoplastic ANS cells (eg, peripheral neuroblastic tumors [pNTs]). We hypothesized that Phox2b immunohistochemical staining (IHC) would also be useful for detecting ENCCs. Methods Hematoxylin and eosin, calretinin IHC, and Phox2b IHC were reviewed on 21 pull-through specimens and on a cohort of 12 rectal biopsies. Results Phox2b IHC demonstrated nuclear positivity in all of the ganglion cells across the different phases of differentiation without background staining. The Phox2b result correlated with the morphological findings, calretinin IHC results, and diagnoses based on the routine diagnostic method. The intensity was uniformly strong in the undifferentiated/immature forms and became variable in the mature forms; this pattern was similar to that seen in pNTs. Conclusion Phox2b IHC was highly sensitive and specific for detecting ganglion cells. It worked especially well for immature ganglion cells, seen in premature neonates, and scattered single forms in transition zones. In basic research settings, Phox2b can be a useful marker for early differentiation of ENCCs.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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Utility of Phox2b immunohistochemical stain in neural crest tumours and non‐neural crest tumours in paediatric patients

Abstract: Phox2b was a specific and sensitive marker for pNT and PCC/PG, especially useful for identifying NB-UD often lacking TH. Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural crest origin.

Cited by 27 publications

References 19 publications

PHOX2B is a reliable immunomarker in distinguishing peripheral neuroblastic tumours from CNS embryonal tumours

PHOX2B is a reliable immunomarker in distinguishing peripheral neuroblastic tumours from CNS embryonal tumours

Phox2b Immunohistochemical Staining in Detecting Enteric Neural Crest Cells in Hirschsprung Disease

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

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