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Despite its clinical significance, the molecular and cellular mechanisms driving carcinogenesis in GBC with PBM remain poorly elucidated. This study investigated the oncogenic mechanisms, biomarkers, and performance associated with Erb-b2 receptor tyrosine kinase 2 (\n                      <jats:italic>ERBB2)<\/jats:italic>\n                      -targeted therapies in GBC with PBM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Overall, 127 surgically treated patients were stratified as follows: Group A, normal gallbladder; Group B, PBM; Group C, GBC without PBM; and Group D, GBC with PBM. We performed whole-exome sequencing (WES) for Group D and human epidermal growth factor receptor 2 immunohistochemistry (HercepTest) for the entire cohort. Fluorescence in situ hybridization (FISH) was used to clarify human epidermal growth factor receptor 2 (HER2) expression in cases with equivocal HercepTest results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplification was detected in 50% of Group D patients. The proportion of HER2 protein expression scores\u2009\u2265\u20092\u2009+\u2009was highest in Group D compared with that in the other groups (50.0% vs. 0% in Groups A and B and 15.6% in Group C) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.006, chi-squared test). Finally, 37.5% and 13.3% of cases in Groups D and C, respectively, showed HER2 overexpression (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.037, chi-squared test).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This is the first evaluation of HER2\/\n                      <jats:italic>ERBB2<\/jats:italic>\n                      expression in GBC with PBM based on WES, HercepTest, and FISH. The significant increase in\n                      <jats:italic>ERBB2<\/jats:italic>\n                      expression, driven by the synergistic interplay between GBC and PBM, underscores a critical molecular interaction that may inform the development of targeted therapeutic strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00535-025-02303-2","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T17:10:02Z","timestamp":1759597802000},"page":"222-238","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Molecular insights into HER2\/ERBB2 amplification and carcinogenesis in gallbladder cancer associated with pancreaticobiliary maljunction"],"prefix":"10.1007","volume":"61","author":[{"given":"Ming","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4582-6589","authenticated-orcid":false,"given":"Daisuke","family":"Douchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taito","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusuke","family":"Migita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Rikiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichiro","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kokumai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Yoshimachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kusaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Shimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Iseki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimpei","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Ohtsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Mizuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Masamune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Furukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiaki","family":"Unno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,4]]},"reference":[{"key":"2303_CR1","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1007\/s00428-019-02706-6","volume":"476","author":"T Albrecht","year":"2020","unstructured":"Albrecht T, Rausch M, Roessler S, et al. 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