Prevalence and influence on outcome of HER2/neu, HER3 and NRG1 expression in patients with metastatic colorectal cancer

Our aim was to explore the impact of the HER2/neu, HER3 receptor as well as their ligands’ neuregulin (NRG1) expression on the outcome of patients with metastatic colorectal cancer (mCRC). NRG1, HER2/neu and HER3 expression was evaluated in 208 patients with mCRC receiving 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as the first-line treatment. Biomarker expression was correlated with the outcome of patients. NRG1 (low192 vs. high16), HER2/neu (low201 vs. high7) and HER3 (low69 vs. high139) expressions were assessed in 208 patients. High versus low NRG1 expression significantly affected progression-free survival (PFS) [4.7 vs. 8.2 months, hazard ratio (HR)2.45; 95% confidence interval (CI)1.45–4.13; P=0.001], but not overall survival (OS) (15.5 vs. 20.7 months, HR1.33; 95% CI0.76–2.35; P=0.32). High versus low HER3 expression (PFS7.1 vs. 8.8 months, HR1.11; 95% CI0.82–1.50; P=0.50; OS19.8 vs. 21.1 months, HR0.95; 95% CI0.70–1.30; P=0.75) and high compared with low HER2/neu expression (PFS7.7 vs. 8.0 months, HR1.07; 95% CI0.71–1.60; P=0.75; OS16.6 vs. 21.1 months, HR1.13; 95% CI0.75–1.71; P=0.57) did not influence outcome. High NRG1 expression was associated with inferior PFS in the FIRE-1 trial. We did not detect a prognostic impact of HER2/neu and HER3 overexpression in mCRC. The frequency of overexpression was comparable with other studies.