title: A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status.
abstract: 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.
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. nhiraoka@ncc.go.jp.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Fluorescence in situ hybridization; Gallbladder cancer; HER2; Heterogeneity; Immunohistochemistry