{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:02:52Z","timestamp":1791284572058,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"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":[[2020,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Special AT\u2010rich sequence\u2010binding protein 2 (SATB2) is a transcriptional regulator with critical roles in brain, craniofacial and skeletal development. It has emerged as a key marker of lower gastrointestinal (GI) tract columnar epithelial and osteoblastic differentiation. Transcription factor immunohistochemistry is useful in assigning site of origin in well\u2010differentiated neuroendocrine tumours (NETs), and has had a limited role in poorly differentiated neuroendocrine carcinomas (NECs). This study sought to evaluate the role of SATB2 in assigning site of origin in neuroendocrine epithelial neoplasms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Tissue microarrays were constructed from the following: 317 NETs (37 thyroid, 46 lung, 16 stomach, 12 duodenum, 70 pancreas, 106 jejunoileum, 24 appendix, and six rectosigmoid), 44 phaeochromocytomas\/paragangliomas, and 79 NECs (29 Merkel cell, 30 lung, and 20 extrapulmonary visceral); nine appendiceal and 19 rectal NETs were examined in whole sections. SATB2 immunohistochemistry was scored for extent (%) and intensity (0\u20133+), with an H\u2010score being calculated. SATB2 was expressed by 96% of rectosigmoid NETs, 79% of appendiceal NETs, and only 7% of other well\u2010differentiated neoplasms (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Expression in lower GI tract NETs (median H\u2010score of 255) was stronger than in other positive tumours (median H\u2010score of 7) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Any SATB2 expression was 86% sensitive\/93% specific for lower GI tract origin. SATB2 was expressed by 79% of Merkel cell carcinomas (median H\u2010score of 300), 33% of lung NECs (median H\u2010score of 23), and 60% of extrapulmonary visceral NECs (median H\u2010score of 110), with stronger expression in Merkel cell carcinoma (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). At an H\u2010score cutoff of \u2265150, SATB2 was 69% sensitive\/90% specific for Merkel cell carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SATB2 is frequently and strongly expressed by lower GI tract NETs; we have adopted it as our rectal NET marker. Relatively frequent and strong expression in Merkel cell carcinoma may have value in assigning NEC site of origin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13943","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T17:53:00Z","timestamp":1561485180000},"page":"251-264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["SATB2 in neuroendocrine neoplasms: strong expression is restricted to well\u2010differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-6379","authenticated-orcid":false,"given":"Andrew M","family":"Bellizzi","sequence":"first","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 Cancer Program University of Iowa Hospitals and Clinics and Holden Comprehensive Cancer Center Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0b013e3182a2dc67"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.4377"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e3181ebb168"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0000000000000850"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2014.08.008"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000563"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e3181ebb56f"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.0077"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2017.12.51"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809064"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2013.06.003"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg248"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1153003"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.03897.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-005-9012-8"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31821c3dae"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000001"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPWW2URZ9JKQJU"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31825d532d"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.2010.10"},{"key":"e_1_2_9_22_1","first-page":"7072","article-title":"SATB2 is a sensitive marker for lower gastrointestinal well\u2010differentiated neuroendocrine tumors","volume":"8","author":"Li Z","year":"2015","journal-title":"Int. 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