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

Abstract

Background: 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.

Methods: The 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.

Results: Positive 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).

Conclusion: The 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 slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9365749431029643.

Figure 1

HER2 expression as detected by IHC and FISH in discordant cases where HER2 status was positive in the LNM but negative in the PGC. (A) FISH-positive LNM sample. (B) IHC-positive LNM sample. (C) FISH-negative PGC sample. (D) IHC-negative PGC sample.

Figure 2

HER2 expression as detected by IHC and FISH in discordant cases, where HER2 status was positive in the PGC but negative in the LNM. (A) FISH-negative LNM sample. (B) IHC-negative LNM sample. (C) FISH-positive PGC sample. (D) IHC-positive PGC sample.