{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:45:08Z","timestamp":1778895908635,"version":"3.51.4"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T00:00:00Z","timestamp":1513814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study evaluated the utility of Phox2b in paediatric tumours. Previously, tyrosine hydroxylase (<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>) was the most widely utilised sympathoadrenal marker specific for neural crest tumours with neuronal\/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Phox2b immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>) was performed on 159 paediatric tumours, including (group 1) 65 neural crest tumours with neuronal differentiation [peripheral neuroblastic tumours (<jats:styled-content style=\"fixed-case\">pNT<\/jats:styled-content>)]: 15 neuroblastoma undifferentiated (<jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">UD<\/jats:styled-content>), 10 <jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content> poorly differentiated (<jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>), 10 <jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content> differentiating (<jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010D), 10 ganglioneuroblastoma intermixed (<jats:styled-content style=\"fixed-case\">GNB<\/jats:styled-content>i), 10 <jats:styled-content style=\"fixed-case\">GNB<\/jats:styled-content> nodular (<jats:styled-content style=\"fixed-case\">GNB<\/jats:styled-content>n) and 10 ganglioneuroma (<jats:styled-content style=\"fixed-case\">GN<\/jats:styled-content>); (group 2) 23 neural crest tumours with neuroendocrine differentiation [pheochromocytoma\/paraganglioma (<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PG<\/jats:styled-content>)]; (group 3) 27 other neural crest tumours including one composite rhabdomyosarcoma\/neuroblastoma; and (group 4) 44 non\u2010neural crest tumours. <jats:styled-content style=\"fixed-case\">TH IHC<\/jats:styled-content> was performed on groups 1, 2 and 3. Phox2b was expressed diffusely in <jats:styled-content style=\"fixed-case\">pNT<\/jats:styled-content> (<jats:italic>n<\/jats:italic> = 65 of 65), strongly in <jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">UD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> and with less intensity in <jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010D, <jats:styled-content style=\"fixed-case\">GNB<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GN<\/jats:styled-content>. Diffuse <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> was seen in all <jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> NB<\/jats:styled-content>\u2010D, <jats:styled-content style=\"fixed-case\">GNB<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GN<\/jats:styled-content>, but nine of 15 <jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">UD<\/jats:styled-content> and a nodule in <jats:styled-content style=\"fixed-case\">GNB<\/jats:styled-content>n did not express <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> (<jats:italic>n<\/jats:italic> = 55 of 65). <jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PG<\/jats:styled-content> expressed diffuse Phox2b (<jats:italic>n<\/jats:italic> = 23 of 23) and diffuse <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>, except for one tumour (<jats:italic>n<\/jats:italic> = 22 of 23). In composite rhabdomyosarcoma, <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumours were negative for Phox2b (<jats:italic>n<\/jats:italic> = none of 44).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Phox2b was a specific and sensitive marker for <jats:styled-content style=\"fixed-case\">pNT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PG<\/jats:styled-content>, especially useful for identifying <jats:styled-content style=\"fixed-case\">NB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">UD<\/jats:styled-content> often lacking <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>. Our study also presented a composite rhabdomyosarcoma\/neuroblastoma of neural crest origin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13412","type":"journal-article","created":{"date-parts":[[2017,10,7]],"date-time":"2017-10-07T15:36:39Z","timestamp":1507390599000},"page":"685-696","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Utility of Phox2b immunohistochemical stain in neural crest tumours and non\u2010neural crest tumours in paediatric patients"],"prefix":"10.1111","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-3835","authenticated-orcid":false,"given":"Mikako","family":"Warren","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital Los Angeles Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Matsuno","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital Los Angeles Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital Los Angeles Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Hospital Los Angeles Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2623-09.2009"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.01.007"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.056747"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31825a6895"},{"key":"e_1_2_6_6_1","first-page":"985","article-title":"PHOX2A and PHOX2B genes are highly co\u2010expressed in human neuroblastoma","volume":"33","author":"Longo L","year":"2008","journal-title":"Int. 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