{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:20:18Z","timestamp":1773332418876,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T00:00:00Z","timestamp":1563408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lymphoepithelioma\u2010like hepatocellular carcinoma (LEL\u2010HCC) is a distinct variant of HCC that is characterized by dense tumor\u2010infiltrating lymphocytes (TILs). Patients with LEL\u2010HCC also show better clinical outcomes compared to conventional HCC (c\u2010HCC), which is commonly presented with low TIL. Emerging evidence has begun to highlight tumor\u2010intrinsic genetic abnormalities in the tumor\u2013host immune interfaces. However, genome\u2010wide characterization of LEL\u2010HCC remains largely unexplored. Here, we defined the genomic landscape of 12 LEL\u2010HCC using whole\u2010exome sequencing, and further underpinned those genetic alterations related to an immune active microenvironment by comparing findings to 15 c\u2010HCC that were sequenced in parallel. Overall, the mutational load between LEL\u2010HCC and c\u2010HCC was similar. Interestingly, SNV incidences of specific genes (<jats:italic>CTNNB1<\/jats:italic>, <jats:italic>AXIN1<\/jats:italic>, <jats:italic>NOTCH1<\/jats:italic>, and <jats:italic>NOTCH2<\/jats:italic>) were significantly higher in c\u2010HCC than LEL\u2010HCC, suggesting a plausible link between activated Wnt\/\u03b2\u2010catenin and Notch signaling pathways and immune avoidance. Marked focal amplification of chromosome 11q13.3 was prevalent in LEL\u2010HCC. Using The Cancer Genome Atlas dataset, we further established oncogenes expressed from chromosome 11q13.3 (<jats:italic>CCND1<\/jats:italic>, <jats:italic>FGF19<\/jats:italic>, and <jats:italic>FGF4<\/jats:italic>) to be strongly associated with the immune checkpoint signature (<jats:italic>CD274<\/jats:italic>, <jats:italic>PDCD1<\/jats:italic>, <jats:italic>BTLA<\/jats:italic>, <jats:italic>CTLA4<\/jats:italic>, <jats:italic>HAVCR2<\/jats:italic>, <jats:italic>IDO1<\/jats:italic>, and <jats:italic>LAG3<\/jats:italic>). Our results have illustrated for the first time the somatic landscape of LEL\u2010HCC, and highlighted molecular alterations that could be exploited in combinatory therapy with checkpoint inhibitors in targeting HCC. \u00a9 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5313","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T21:59:55Z","timestamp":1559771995000},"page":"166-172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Genomic landscape of lymphoepithelioma\u2010like hepatocellular carcinoma"],"prefix":"10.1002","volume":"249","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-163X","authenticated-orcid":false,"given":"Anthony W\u2010H","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Anatomical and Cellular Pathology Sir YK Pao Centre for Cancer, Hong Kong SAR  PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology Sir YK Pao Centre for Cancer, Hong Kong SAR  PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charing C\u2010N","family":"Chong","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery The Chinese University of Hong Kong  Hong Kong SAR PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith K\u2010Y","family":"Tin","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology Sir YK Pao Centre for Cancer, Hong Kong SAR  PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chit","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology Sir YK Pao Centre for Cancer, Hong Kong SAR  PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology Sir YK Pao Centre for Cancer, Hong Kong SAR  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