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Because intra\u2010 (i<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content>) and extrahepatic (e<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content>) cholangiocarcinoma display such differences, we performed a systematic review and meta\u2010analysis to analyze differences in the immunohistochemical profile of these tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>ebruary 2014, we searched the two main medical literature databases <jats:styled-content style=\"fixed-case\">MEDLINE<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EMBASE<\/jats:styled-content>. We extracted risk ratios and 95% confidence intervals from the identified studies and performed random\u2010effects model meta\u2010analyses in accordance with <jats:styled-content style=\"fixed-case\">PRISMA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">REMARK<\/jats:styled-content> guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 54 cohort studies, including 4458 patients and studying 102 individual markers met the inclusion criteria. Of the 57 markers that were evaluated in more than 30 i<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content> and e<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content> patients, 18 showed a statistically significant difference in expression between i<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content> and e<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content>. Biomarkers expressed differently between i<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content> and e<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content> included potential targets of therapy: <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>, c\u2010erbB\u20102 and <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>. Several markers showed no statistical difference but large 95% confidence intervals, suggesting insufficient sample size.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This systematic review shows differences in marker expression between i<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content> and e<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content>. Consequently, patients with i<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content> and e<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content> may benefit from different treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12620","type":"journal-article","created":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T07:17:33Z","timestamp":1399015053000},"page":"1582-1594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["<b>Differences in immunohistochemical biomarkers between intra\u2010 and extrahepatic cholangiocarcinoma: A systematic review and meta\u2010analysis<\/b>"],"prefix":"10.1111","volume":"29","author":[{"given":"Jimme K.","family":"Wiggers","sequence":"first","affiliation":[{"name":"Department of Surgery Academic Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Ruys","sequence":"additional","affiliation":[{"name":"Department of Surgery Academic Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas","family":"Groot Koerkamp","sequence":"additional","affiliation":[{"name":"Department of Surgery Academic Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Beuers","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiebo J.","family":"ten Kate","sequence":"additional","affiliation":[{"name":"Department of Pathology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M","family":"van Gulik","sequence":"additional","affiliation":[{"name":"Department of Surgery Academic Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,29]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"American Joint Committee on Cancer: AJCC Cancer Staging Manual","author":"Edge SB","year":"2009"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908721"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67530-7"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds077"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-013-3286-x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.03.017"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.6631"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.01.0454"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp038"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-3284"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.110"},{"key":"e_1_2_6_13_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [Updated September 2009]","author":"Higgins JP","year":"2009"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.01.008"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"e_1_2_6_18_1","first-page":"1234","article-title":"Caveolin\u2010I overexpression is a favourable prognostic factor for patients with extrahepatic bile duct carcinoma","volume":"88","author":"Murakami S","year":"2003","journal-title":"Br. 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