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We also intended to explore the clinical pathological characteristics, molecular features, RNA expression and immune microenvironment of HER2-positive ICC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed a cohort of 304 ICCs using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to identify HER2 status. Comprehensive analyses of the clinicopathological, molecular genetic, and RNA expression characterizations of ICCs with varying HER2 statuses were performed using next-generation sequencing. We further investigated the tumor microenvironment of ICCs with different HER2 statuses using IHC and multiplex immunofluorescence staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HER2\/CEP17 ratio of\u2009\u2265\u20092.0 and HER2 copy number\u2009\u2265\u20094.0; or HER2 copy number\u2009\u2265\u20096.0 were setup as FISH positive criteria. Based on this criterion, 13 (4.27%, 13\/304) samples were classified as having HER2 amplification. The agreement between FISH and IHC results in ICC was poor. HER2-amplified cases demonstrated a higher tumor mutational burden compared to non-amplified cases. No significant differences were observed in immune markers between the two groups. However, an increased density of CD8\u2009+\u2009CTLA4\u2009+\u2009and CD8\u2009+\u2009FOXP3\u2009+\u2009cells was identified in HER2 gene-amplified cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FISH proves to be more appropriate as the gold standard for HER2 evaluation in ICC. HER2 gene-amplified ICCs exhibit poorer prognosis, higher mutational burden, and T cell exhaustion and immune suppressed microenvironment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-024-05894-0","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T16:17:21Z","timestamp":1724861841000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["HER2 amplification subtype intrahepatic cholangiocarcinoma exhibits high mutation burden and T cell exhaustion microenvironment"],"prefix":"10.1007","volume":"150","author":[{"given":"Xiaohong","family":"Pu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beicheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"5894_CR1","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1309\/AJCPXTZSKBRIP07W","volume":"136","author":"KH Allison","year":"2011","unstructured":"Allison KH, Dintzis SM, Schmidt RA (2011) Frequency of HER2 heterogeneity by fluorescence in situ hybridization according to CAP expert panel recommendations: time for a new look at how to report heterogeneity. 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