{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:24:12Z","timestamp":1792113852936,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T00:00:00Z","timestamp":1499904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 CA174521\u201001A1"],"award-info":[{"award-number":["P50 CA174521\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Paired\u2010like homeobox 2b (<jats:styled-content style=\"fixed-case\">PHOX<\/jats:styled-content>2B) is a transcription factor with expression outside of the central nervous system restricted to neurons and chromaffin cells of the autonomic nervous system. Germline mutations cause congenital central hypoventilation syndrome and predispose to neuroblastoma and Hirschsprung disease. Among paediatric small round cell tumours, <jats:styled-content style=\"fixed-case\">PHOX<\/jats:styled-content>2B is neuroblastoma\u2010specific. Two studies of adult autonomic nervous system tumours (<jats:italic>n<\/jats:italic> = 62) produced conflicting results (all tumours stained in one; expression restricted to 40% of paragangliomas in the other). We examined <jats:styled-content style=\"fixed-case\">PHOX<\/jats:styled-content>2B expression in a large cohort of phaeochromocytomas and paragangliomas, as well as well\u2010differentiated neuroendocrine tumours (<jats:styled-content style=\"fixed-case\">WDNET<\/jats:styled-content>s) and poorly differentiated neuroendocrine carcinomas (<jats:styled-content style=\"fixed-case\">PDNEC<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Tissue microarrays (<jats:styled-content style=\"fixed-case\">TMA<\/jats:styled-content>s) were constructed from 609 tumours: 111 phaeochromocytomas, 146 paragangliomas, 250 <jats:styled-content style=\"fixed-case\">WDNET<\/jats:styled-content>s, and 102 <jats:styled-content style=\"fixed-case\">PDNEC<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">PHOX<\/jats:styled-content>2B immunohistochemistry was scored for extent (%) and intensity (0\u20133+), and an H\u2010score (extent \u00d7 intensity) was calculated. <jats:styled-content style=\"fixed-case\">PHOX<\/jats:styled-content>2B expression was seen in 32% of phaeochromocytomas and in 47% of paragangliomas. Mean\/median H\u2010scores for these tumours were in the 30\u201355 range (i.e. weak to moderate staining). No <jats:styled-content style=\"fixed-case\">WDNET<\/jats:styled-content>s and only 7% of <jats:styled-content style=\"fixed-case\">PDNEC<\/jats:styled-content>s stained, the latter often strongly. In a representative cohort of corresponding whole sections (<jats:italic>n<\/jats:italic> = 55), the results in <jats:styled-content style=\"fixed-case\">WDNET<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">PDNEC<\/jats:styled-content>s were unchanged, whereas half of the phaeochromocytomas\/paragangliomas that were negative on <jats:styled-content style=\"fixed-case\">TMA<\/jats:styled-content>s became focally, weakly positive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We found frequent, weak to moderate <jats:styled-content style=\"fixed-case\">PHOX<\/jats:styled-content>2B expression in phaeochromocytomas\/paragangliomas and no expression in <jats:styled-content style=\"fixed-case\">WDNET<\/jats:styled-content>s, which could be diagnostically useful in the distinction of these tumours. Expression in a minority of <jats:styled-content style=\"fixed-case\">PDNEC<\/jats:styled-content>s probably reflects the transcription factor lineage infidelity that is characteristic of this tumour class.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13243","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T17:41:24Z","timestamp":1493746884000},"page":"503-510","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Examination of <scp>PHOX<\/scp>2B in adult neuroendocrine neoplasms reveals relatively frequent expression in phaeochromocytomas and paragangliomas"],"prefix":"10.1111","volume":"71","author":[{"given":"John P","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pathology University of Iowa Hospitals and Clinics and Carver College of Medicine Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin P","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M","family":"O'Dorisio","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Iowa Hospitals and Clinics and Carver College of Medicine Iowa City IA USA"},{"name":"University of Iowa Neuroendocrine Tumor Specialized Program of Research Excellence (SPORE) Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Howe","sequence":"additional","affiliation":[{"name":"University of Iowa Neuroendocrine Tumor Specialized Program of Research Excellence (SPORE) Iowa City IA USA"},{"name":"Department of Surgery University of Iowa Hospitals and Clinics and Carver College of Medicine Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6475-8345","authenticated-orcid":false,"given":"Jason L","family":"Hornick","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-6379","authenticated-orcid":false,"given":"Andrew M","family":"Bellizzi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Iowa Hospitals and Clinics and Carver College of Medicine Iowa City IA USA"},{"name":"University of Iowa Neuroendocrine Tumor Specialized Program of Research Excellence (SPORE) Iowa City IA 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