{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T01:14:04Z","timestamp":1778721244583,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T00:00:00Z","timestamp":1530662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006823","name":"Boston Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"Aims<\/jats:title>The PHOX<\/jats:styled-content>2B<\/jats:italic> gene regulates neuronal maturation in the brain stem nuclei associated with cardiorespiratory function and in the autonomic sympathetic and enteric nervous system. PHOX<\/jats:styled-content>2B expression is a reliable immunomarker for peripheral neuroblastic tumours; however, no systematic evaluation of central nervous system (CNS<\/jats:styled-content>) embryonal tumours was included in the studies. We encountered two cases in which the differential diagnosis included neuroblastoma and CNS<\/jats:styled-content> embryonal tumour, and we hypothesised that PHOX<\/jats:styled-content>2B immunostain would be helpful in establishing the diagnosis.<\/jats:p><\/jats:sec>Methods and results<\/jats:title>PHOX<\/jats:styled-content>2B immunostain was performed on 29 paediatric cases, with adequate controls: one retroperitoneal embryonal tumour in a child with retinoblastoma (index 1), one posterior fossa embryonal tumour in a child with a neuroblastoma (index 2), seven medulloblastomas, four atypical teratoid\/rhabdoid tumours (ATRT<\/jats:styled-content>), four retinoblastomas, six pineoblastomas, four embryonal tumours with multilayered rosettes (ETMR<\/jats:styled-content>) and two CNS<\/jats:styled-content> embryonal tumours, not elsewhere classified. Cell lineage immunomarkers (GFAP<\/jats:styled-content>, OLIG<\/jats:styled-content>2, synaptophysin, NeuN, CRX<\/jats:styled-content>, PGP<\/jats:styled-content> 9.5), immunosurrogates for molecular alterations (beta\u2010catenin, INI<\/jats:styled-content>1, Lin\u201028), array CGH<\/jats:styled-content> and OncoPanel were performed as needed. Medulloblastomas, ATRT<\/jats:styled-content>s, ETMR<\/jats:styled-content>s, retinoblastomas and CNS<\/jats:styled-content> embryonal tumours not elsewhere classified were essentially negative for PHOX<\/jats:styled-content>2B. Two of six pineoblastomas had significant PHOX<\/jats:styled-content>2B expression, while the rest were negative. Index 1 was negative for PHOX<\/jats:styled-content>2B and PGP<\/jats:styled-content> 9.5 and positive for CRX<\/jats:styled-content>, consistent with retinoblastoma. Index 2 had diffuse PHOX<\/jats:styled-content>2B expression, MYCN<\/jats:styled-content> amplification and no copy number changes of medulloblastoma, in keeping with neuroblastoma.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>PHOX<\/jats:styled-content>2B antibody is helpful in distinguishing between peripheral neuroblastic and CNS<\/jats:styled-content> embryonal tumours, which are immunonegative, with the caveat that a subset of pineoblastomas has significant expression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13648","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T23:46:00Z","timestamp":1526341560000},"page":"483-491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PHOX<\/scp>2B is a reliable immunomarker in distinguishing peripheral neuroblastic tumours from CNS<\/scp> embryonal tumours"],"prefix":"10.1111","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9246-4184","authenticated-orcid":false,"given":"Sanda","family":"Alexandrescu","sequence":"first","affiliation":[{"name":"Department of Pathology Boston Children's Hospital Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Paulson","sequence":"additional","affiliation":[{"name":"Department of Pathology Boston Children's Hospital Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Dubuc","sequence":"additional","affiliation":[{"name":"Center for Advanced Molecular Diagnostics Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azra","family":"Ligon","sequence":"additional","affiliation":[{"name":"Center for Advanced Molecular Diagnostics Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hart G","family":"Lidov","sequence":"additional","affiliation":[{"name":"Department of Pathology Boston Children's Hospital Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,7,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/20700"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0826"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00866"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.679027"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23365"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38162"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31278"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210659"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/383253"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807309242"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"10627","DOI":"10.18632\/oncotarget.7056","article-title":"PHOX2B is a suppressor of neuroblastoma metastasis","volume":"7","author":"Naftal O","year":"2016","journal-title":"Oncotarget"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19922"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31825a6895"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13288"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13412"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182601d84"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2016.09.061"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1808-0"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nov015"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007887"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2015.3088"},{"key":"e_1_2_7_23_1","first-page":"985","article-title":"Phox2A and PHOX2B genes are highly expressed in human neuroblastoma","volume":"33","author":"Longo L","year":"2008","journal-title":"Int. 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