Background: EGFR overexpression is a prognostic biomarker and is expected to be a predictive biomarker for anti-EGFR therapies in gastric cancer. However, few studies have reported the clinical impact of EGFR gene copy number (GCN) and its correlation with EGFR overexpression.
Methods: We used dual in situ hybridization (DISH) to detect EGFR GCN and chromosome 7 centromere (CEN7) in a set of tissue microarrays representing 855 patients with gastric cancer. These data were compared with those of immunohistochemical (IHC) analysis of EGFR expression to evaluate prognostic value.
Results: EGFR GCN gain (≥ 2.5 EGFR signals per cell) was detected in 194 patients (22.7%) and indicated poor prognosis. Among 194 patients, EGFR amplification (EGFR/CEN7 ≥ 2.0) was observed in 29 patients (14.9%), which was almost identical to the IHC 3+ subgroup and worst prognostic subgroup. Patients with EGFR GCN gain but not amplification, including those exhibiting polysomy, also exhibited poorer prognosis than GCN non-gain patients and were distributed between IHC 0/1+ and 2+ subgroups. GCN gain was frequently observed in patients with more advanced disease, but served as an independent prognostic factor regardless of the pathological stage.
Conclusions: EGFR GCN gain is a more accurate prognostic biomarker than EGFR overexpression in patients with gastric cancer.
Keywords: Amplification; Dual in situ hybridization; EGFR; Gastric cancer; Gene copy number.