Impact of Expression of Human Epidermal Growth Factor Receptors EGFR and ERBB2 on Survival in Stage II/III Gastric Cancer

Purpose: EGF receptor (EGFR) and HER2 positivity are considered to be negative prognostic factors in gastric cancer. Biomarker analysis was conducted to evaluate the impact of EGFR and HER2 expression on the outcome of patients enrolled in the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC), a randomized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer. Experimental Design: Formalin-fixed, paraffin-embedded surgical specimens were retrospectively examined in 829 patients (78.3%). The effects of EGFR and HER2 positivity on survival were analyzed on the basis of the 5-year survival data from the study. EGFR positivity was defined as an immunohistochemistry (IHC) score of 3+, and HER2 positivity as an IHC score of 3+ or an IHC score of 2+ with a positive dual-color in situ hybridization status. Results: EGFR and HER2 were positive in 75 (9.0%) and 113 (13.6%) patients, respectively. The overall and relapse-free survival rates were significantly lower in EGFR-positive patients than in EGFR-negative patients, whereas they were similar in HER2-positive and HER2-negative patients. Multivariate analysis showed that EGFR positivity correlated with poor outcomes [HR = 1.504; 95% confidence interval (CI) = 1.020-2.149; P = 0.040]. Treatment with S-1 improved survival compared with surgery alone, irrespective of EGFR and HER2 status. Conclusions: EGFR positivity, but not HER2 positivity, was associated with poor patient outcomes after curative resection of stage II/III gastric cancer. There was no interaction between S-1 and EGFR or HER2 status with respect to survival outcome. Clin Cancer Res; 18(21); 5992-6000. (C) 2012 AACR.