A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status

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 o...

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Bibliographic Details
Published in:Virchows Archiv : an international journal of pathology 2016-04, Vol.468 (4), p.431-439
Main Authors: Yoshida, Hiroshi, Shimada, Kazuaki, Kosuge, Tomoo, Hiraoka, Nobuyoshi
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - analysis
Carcinoma - genetics
Carcinoma - pathology
Female
Gallbladder Neoplasms - genetics
Gallbladder Neoplasms - pathology
Gene Amplification
Heterogeneity
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Male
Medicine
Medicine & Public Health
Middle Aged
Original Article
Pathology
Receptor, ErbB-2 - analysis
Receptor, ErbB-2 - biosynthesis
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Summary: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.
ISSN:0945-6317
1432-2307
DOI:10.1007/s00428-015-1898-1