{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:49:07Z","timestamp":1770140947789,"version":"3.49.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Adenocarcinomas of the biliary tract frequently present diagnostic challenges because of their histologic overlap with benign and preinvasive lesions. The molecular profiles of biliary adenocarcinomas vary by anatomical location. Variations in IDH1\/2, common in intrahepatic cholangiocarcinoma, can lead to defective production of 5-hydroxymethylcytosine (5-hmC). Limited ancillary studies are available for biliary adenocarcinomas, and loss of 5-hmC staining could serve as a helpful ancillary diagnostic tool for biliary tract malignancies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated 93 cases\u201420 benign biliary lesions, 15 preinvasive biliary neoplasms, 46 invasive biliary carcinomas, and 12 pancreatic adenocarcinomas\u2014for 5-hmC staining. Preoperative biopsies from 16 cases of biliary carcinoma were also stained. Sixteen nonneoplastic\/reactive bile duct biopsies served as controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Loss of 5-hmC was seen in 41 of 46 (89.1%) biliary malignancies vs 0 of 20 benign tumors (P\u2009&amp;lt;\u2009.001), for a sensitivity and specificity of 89.1% and 100%, respectively. Intrahepatic cholangiocarcinoma showed loss of 5-hmC in 11 of 13 (84.6%) cases, similar to the 30 of 33 (90.9%) cases in other biliary adenocarcinomas (P\u2009=\u2009.61). Similarly, 5-hmC loss was more frequent in distal bile duct adenocarcinomas than in pancreatic ductal adenocarcinomas, at 15 of 17 (88.2%) vs 4 of 12 (33.3%), respectively (P\u2009=\u2009.0045). There was no difference in the frequency of 5-hmC loss in patients that received neoadjuvant therapy vs those who did not (90.9% vs 88.6%, P\u2009 &amp;gt; .99). 5-hmC immunohistochemistry in preoperative biopsies was concordant with the resection specimen in 81.3% (13\/16) of cases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Loss of 5-hmC is not unique to intrahepatic cholangiocarcinoma among biliary carcinomas, but is a useful diagnostic marker differentiating malignancies of the biliary tree from benign mimics.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajcp\/aqae001","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T13:34:39Z","timestamp":1707744879000},"page":"41-50","source":"Crossref","is-referenced-by-count":1,"title":["5-Hydroxymethylcytosine (5-hmC) loss is a marker of malignancy in biliary neoplasms"],"prefix":"10.1093","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7251-5984","authenticated-orcid":false,"given":"Miguel S","family":"Gonzalez-Mancera","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Siref","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-4054","authenticated-orcid":false,"given":"Kambiz","family":"Kosari","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Nissen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivas","family":"Gaddam","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Hendifar","sequence":"additional","affiliation":[{"name":"Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arsen","family":"Osipov","sequence":"additional","affiliation":[{"name":"Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2140-3514","authenticated-orcid":false,"given":"Kevin","family":"Waters","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Hutchings","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4864-6498","authenticated-orcid":false,"given":"Maha","family":"Guindi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8116-1089","authenticated-orcid":false,"given":"Brent K","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , US"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,2,12]]},"reference":[{"key":"2024070505520088500_CIT0001","first-page":"1215","article-title":"Pathogenesis, diagnosis, and management of cholangiocarcinoma","volume-title":"Gastroenterology","author":"Rizvi","year":"2013"},{"key":"2024070505520088500_CIT0002","first-page":"95","article-title":"Cholangiocarcinoma\u2014evolving concepts and therapeutic strategies","volume-title":"Nat Rev Clin Oncol.","author":"Rizvi","year":"2018"},{"key":"2024070505520088500_CIT0003","first-page":"7","article-title":"Anatomical, histomorphological and molecular classification of cholangiocarcinoma","volume-title":"Liver Int.","author":"Kendall","year":"2019"},{"key":"2024070505520088500_CIT0004","first-page":"1358","article-title":"Intrapancreatic distal common bile duct carcinoma: analysis, staging considerations, and comparison with pancreatic ductal and ampullary adenocarcinomas","volume-title":"Mod. 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