{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:02:13Z","timestamp":1793037733227,"version":"4.5.0"},"reference-count":28,"publisher":"BMJ","issue":"6","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2024,2,27]]},"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:p>\n                    Paired-like homeobox 2B (\n                    <jats:italic>PHOX2B<\/jats:italic>\n                    ) is a gene essential in the development of the autonomic nervous system.\n                    <jats:italic>PHOX2B<\/jats:italic>\n                    mutations are associated with neurocristopathies\u2014Hirschsprung disease (HSCR) and congenital central hypoventilation syndrome (CCHS)\u2014and peripheral neuroblastic tumours. PHOXB2 plays an important role in the diagnostics of these conditions.\n                  <\/jats:p>\n                  <jats:p>\n                    Genotyping of a\n                    <jats:italic>PHOX2B<\/jats:italic>\n                    pathogenic variant is required to establish a diagnosis of CCHS. In HSCR patients, PHOX2B immunohistochemical staining has proven to be a valuable tool in identifying this disease. Furthermore,\n                    <jats:italic>PHOXB2<\/jats:italic>\n                    is a predisposition gene for neuroblastoma, in which PHOX2B immunohistochemical staining can be used as a highly sensitive and specific diagnostic marker. The utility of PHOX2B immunohistochemistry in pheochromocytoma and paraganglioma has also been studied but yields conflicting results.\n                  <\/jats:p>\n                  <jats:p>\n                    In this review, an overview is given of\n                    <jats:italic>PHOX2B<\/jats:italic>\n                    , its associated diseases and the usefulness of PHOX2B immunohistochemistry as a diagnostic tool.\n                  <\/jats:p>","DOI":"10.1136\/jcp-2023-209047","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T13:20:50Z","timestamp":1709904050000},"page":"378-382","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["PHOX2B: a diagnostic cornerstone in neurocristopathies and neuroblastomas"],"prefix":"10.1136","volume":"77","author":[{"given":"Mei-Lan","family":"Windels","sequence":"first","affiliation":[{"name":"Department of Pathology, Ghent University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0876-3398","authenticated-orcid":false,"given":"Fleur","family":"Cordier","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ghent University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Van Dorpe","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ghent University Hospital, Ghent, Belgium"},{"name":"Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth","family":"Ferdinande","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ghent University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6064-1673","authenticated-orcid":false,"given":"David","family":"Creytens","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ghent University Hospital, Ghent, Belgium"},{"name":"Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"2025112110284991000_77.6.378.1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/his.13648","article-title":"Phox2B is a reliable Immunomarker in distinguishing peripheral Neuroblastic tumours from CNS embryonal tumours","volume":"73","author":"Alexandrescu","year":"2018","journal-title":"Histopathology"},{"key":"2025112110284991000_77.6.378.2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/his.13243","article-title":"Examination of Phox2B in adult Neuroendocrine Neoplasms reveals relatively frequent expression in Phaeochromocytomas and Paragangliomas","volume":"71","author":"Lee","year":"2017","journal-title":"Histopathology"},{"key":"2025112110284991000_77.6.378.3","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13633"},{"key":"2025112110284991000_77.6.378.4","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1111\/his.13288","article-title":"Phox2B reliably distinguishes neuroblastoma among small round blue cell tumours","volume":"71","author":"Hung","year":"2017","journal-title":"Histopathology"},{"key":"2025112110284991000_77.6.378.5","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s12022-022-09730-4","article-title":"Phox2B is a sensitive and 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Rep"},{"key":"2025112110284991000_77.6.378.8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/1093526620953372","article-title":"Phox2B immunohistochemical staining in detecting Enteric neural crest cells in Hirschsprung disease","volume":"24","author":"Alturkustani","year":"2021","journal-title":"Pediatr Dev Pathol"},{"key":"2025112110284991000_77.6.378.9","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38218"},{"key":"2025112110284991000_77.6.378.10","unstructured":"Weese-Mayer DE , Rand CM , Khaytin I , et al . Congenital central hypoventilation syndrome 2004. Available: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1427\/ [Accessed 28 Jan 2021]."},{"key":"2025112110284991000_77.6.378.11","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1097\/PAS.0000000000001528","article-title":"Phox2B immunostaining: A simple and helpful tool for the recognition of ganglionic cells and diagnosis of Hirschsprung disease","volume":"44","author":"Drabent","year":"2020","journal-title":"Am J Surg Pathol"},{"key":"2025112110284991000_77.6.378.12","unstructured":"Shimada H . 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Neuroblastoma 2023, Available: https:\/\/tumourclassification.iarc.who.int\/chaptercontent\/44\/326"},{"key":"2025112110284991000_77.6.378.15","doi-asserted-by":"crossref","first-page":"104272","DOI":"10.1016\/j.yexmp.2019.104272","article-title":"The role of \u0392-Catenin and paired-like Homeobox 2B (Phox2B) expression in neuroblastoma patients; predictive and Prognostic value","volume":"110","author":"El-Shazly","year":"2019","journal-title":"Experimental and Molecular Pathology"},{"key":"2025112110284991000_77.6.378.16","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30380"},{"key":"2025112110284991000_77.6.378.17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2174\/1573396314666180129101627","article-title":"Biological and genetic features of neuroblastoma and their clinical importance","volume":"14","author":"Aygun","year":"2018","journal-title":"Curr Pediatr Rev"},{"key":"2025112110284991000_77.6.378.18","first-page":"284","article-title":"Nervous system: embryonal tumors: neuroblastoma","volume":"24","author":"Pudela","year":"2020","journal-title":"Atlas Genet Cytogenet Oncol Haematol"},{"key":"2025112110284991000_77.6.378.19","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-018-2820-3"},{"key":"2025112110284991000_77.6.378.20","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/his.13412","article-title":"Utility of Phox2B immunohistochemical stain in neural crest tumours and non-neural crest tumours in Paediatric patients","volume":"72","author":"Warren","year":"2018","journal-title":"Histopathology"},{"key":"2025112110284991000_77.6.378.21","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1093\/jnen\/nlab112","article-title":"Phox2B as a reliable marker for neuroblastoma in tissue and Cytology specimens","volume":"80","author":"Ma","year":"2021","journal-title":"J Neuropathol Exp Neurol"},{"key":"2025112110284991000_77.6.378.22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/pin.13255","article-title":"Spectrum of paired-like Homeobox 2B Immunoexpression in pediatric brain tumors with embryonal morphology","volume":"72","author":"Alturkustani","year":"2022","journal-title":"Pathol Int"},{"key":"2025112110284991000_77.6.378.23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/gcc.22826","article-title":"Adult-onset neuroblastoma: report of seven cases with molecular genetic characterization","volume":"59","author":"Duan","year":"2020","journal-title":"Genes Chromosomes Cancer"},{"key":"2025112110284991000_77.6.378.24","unstructured":"Tischler AS . Phaeochromocytoma 2022, Available: https:\/\/tumourclassification.iarc.who.int\/chaptercontent\/53\/112"},{"key":"2025112110284991000_77.6.378.25","unstructured":"Tischler AS . Parasympathetic paraganglioma 2022, Available: https:\/\/tumourclassification.iarc.who.int\/chaptercontent\/53\/110"},{"key":"2025112110284991000_77.6.378.26","unstructured":"Tischler AS . 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