Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes

Noriaki Kanamori,Masashi Fujii,Megumu Watanabe,Mitsugu Kochi,Shinobu Masuda,Hiroshi Suda,Tadatoshi Takayama,Hidenori Tamegai,Tomoya Funada,Yoshiaki Mihara

doi:10.1186/1746-1596-8-191

Abstract

BackgroundThe aim of this study was to investigate how differences in expression of HER2 between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents.MethodsThe analysis was conducted in 102 patients who underwent surgical resection for primary gastric cancers (PGCs; adenocarcinoma, intestinal type) with synchronous LNMs. HER2 gene status and protein expression were investigated by immunohistochemistry (IHC) in all patients; fluorescence in situ hybridization (FISH) was performed in 22 patients. The correlation between HER2 gene status in PGCs and their LNMs was evaluated.ResultsPositive HER2 expression as detected by IHC + FISH was observed in 27/102 PGC samples (26.5%) and 29/102 LNM samples (28.4%). HER2 amplification status in 102 paired PGC and LNM samples as evaluated by FISH + IHC was concordant in 92 patients (90.2%), 69 (67.6%) were unamplified and 23/102 (22.5%) were amplified at both sites, and discordant in 10 patients (9.8%), 4 (3.9%) were positive for PGC and negative for LNM, while 6 (5.9%) were positive for LNM and negative for PGC. The results of FISH + IHC showed very strong concordance in HER2 status between the PGC and LNM groups (k = 0.754).ConclusionThe high concordance between HER2 results for PGCs and their LNMs indicates that assessment of HER2 status in the primary cancer alone is a reliable basis for deciding treatment with anti-HER2 agents in patients with LNMs from gastric adenocarcinoma.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9365749431029643.

Highlights

The aim of this study was to investigate how differences in expression of human epidermal growth factor receptor 2 (HER2) between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents
A large number of studies have shown that HER2positivity, which is associated with poor prognosis, is detected in 7% to 34% of patients with gastric cancer [1,2,3,4,5,6,7,8,9]
The HER2 gene copy number was evaluated by IHC in 102 consecutive primary gastric adenocarcinoma specimens and their corresponding metastatic lesions and by fluorescence in situ hybridization (FISH) in 22

Summary

Introduction

The aim of this study was to investigate how differences in expression of HER2 between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents. The efficacy of trastuzumab in metastatic gastric cancer may be influenced by downstream deregulation of HER2 signaling proteins detected in the primary tumor. These earlier data were obtained by analyzing the clinical response in gastric cancer patients with regard to molecular features detected in the primary gastric cancers (PGCs). The level of expression of a particular molecular marker or gene status may differ between a PGC and its corresponding metastatic lesions, and this may affect the clinical significance of predictive tests

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