Quantification of EGFR autoantibodies in the amplification phenomenon of HER2 in breast cancer

摘要

Background: Gene amplification or overexpression of human epidermal growth factor receptor HER2/ErB2 is seen in 25-30% of patients with breast cancer and is related to an aggressive disease. The mechanism behind the HER2 gene amplification is unknown, but it may be caused by continuous stimulation and activation. We hypothesised that autoantibodies against EGFR might have a stimulatory effect. To investigate this we developed a quantitative method to measure autoantibodies against EGFR in serum (S-EGFRAb). Methods: Serum samples from primary breast cancer patients were selected based on the degree of HER2 protein and gene amplification in the cancer tissue. Fifty patients had low levels of HER2 (≤16 ng/mg total protein) and no HER2 gene amplification; 43 patients had high levels of HER2 (≥200 ng/mg total protein) and HER2 gene amplification. Serum was also collected from controls consisting of 50 healthy age-matched women. An ELISA was developed to measure S-EGFRAb quantitatively. Results: No significant differences in S-EGFRAb concentrations were seen between patients with high and low levels of HER2 or between the patients and the controls. Furthermore, no significant correlations were observed between S-EGFRAb and stage, differentiation state, age or prognosis. A negative correlation (p=0.0022) was found between S-EGFRAb and disease free survival in the group of patients with relapse or death. Conclusions: S-EGFRAb can be measured accurately using the ELISA we developed. We conclude that autoantibodies against EGFR do not seem to be associated with the HER2 gene amplification phenomenon.