PMID- 26758058 OWN - NLM STAT- MEDLINE DCOM- 20160822 LR - 20220316 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 468 IP - 4 DP - 2016 Apr TI - A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status. PG - 431-9 LID - 10.1007/s00428-015-1898-1 [doi] AB - Gallbladder cancer (GBC) has a poor prognosis, and new targeted therapeutic options are needed. We investigated the human epidermal growth factor receptor 2 (HER2) status and its clinicopathological significance in a large cohort of GBC patients. We assessed HER2 expression in a consecutive series of 211 GBC cases by immunohistochemistry (IHC), paying particular attention to intratumoral heterogeneity. HER2 gene amplification was analyzed by dual-color fluorescence in situ hybridization (FISH). An HER2 positive status was called when the IHC score was 3+ or when the IHC score was 2+, and FISH was positive. Correlations were analyzed between HER2 status and clinicopathological parameters including survival. The HER2 IHC score was 0 in 144 (68.2%), 1+ in 28 (13.3%), 2+ in 14 (6.6%), and 3+ in 25 cases (11.8%). In 20/39 (51%) of the IHC 2+ and 3+ cases, the staining pattern was heterogeneous. In HER2 IHC score 2+ and 3+ cases, HER2 FISH was positive in 83% (10/12) and 96% (24/25), respectively. Altogether, 35/211 cases (16.6%) were HER2 positive. There was no significant association between HER2 status and clinicopathological variables or survival. We identified a significant subgroup of HER2-positive GBC cases, for whom a clinical trial with anti-HER2 therapy might be considered. FAU - Yoshida, Hiroshi AU - Yoshida H AD - Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. FAU - Shimada, Kazuaki AU - Shimada K AD - Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. FAU - Kosuge, Tomoo AU - Kosuge T AD - Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. FAU - Hiraoka, Nobuyoshi AU - Hiraoka N AD - Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. nhiraoka@ncc.go.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160113 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*analysis MH - Carcinoma/*genetics/pathology MH - Female MH - Gallbladder Neoplasms/*genetics/pathology MH - Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Receptor, ErbB-2/analysis/*biosynthesis OTO - NOTNLM OT - Fluorescence in situ hybridization OT - Gallbladder cancer OT - HER2 OT - Heterogeneity OT - Immunohistochemistry EDAT- 2016/01/14 06:00 MHDA- 2016/08/23 06:00 CRDT- 2016/01/14 06:00 PHST- 2015/06/08 00:00 [received] PHST- 2015/12/28 00:00 [accepted] PHST- 2015/10/24 00:00 [revised] PHST- 2016/01/14 06:00 [entrez] PHST- 2016/01/14 06:00 [pubmed] PHST- 2016/08/23 06:00 [medline] AID - 10.1007/s00428-015-1898-1 [pii] AID - 10.1007/s00428-015-1898-1 [doi] PST - ppublish SO - Virchows Arch. 2016 Apr;468(4):431-9. doi: 10.1007/s00428-015-1898-1. Epub 2016 Jan 13.