EGFR Protein Expression of KRAS Wild-Type Colorectal Cancer: Predictive Value of the Sidedness for Efficacy of Anti-EGFR Therapy.

Abstract

Right- and left-sided colorectal cancers (RSCRC and LSCRC, respectively) are different developmentally, genetically and prognostically. Clinical data also indicate that they respond differently to anti-EGFR therapies. The role of EGFR protein expression in KRAS wild type colorectal cancer is also controversial. Here we have used a cohort of anti-EGFR antibody treated KRAS-wild type colorectal cancer patients (n = 97) to analyse the prognostic role of EGFR protein expression in relation to sidedness. In our cohort EGFR copy number, determined by FISH, was not associated with the level of EGFR protein, assessed by immunohistochemistry and measured by H-scoring. There was a significantly higher EGFR H-score detected in RSCRC as compared to LSCRC in primary tumors (p = 0.04). Furthermore, in a proportion of cases (n = 31) metastatic tissues were also available and their analysis also found a significantly higher EGFR H-score in metastases of RSCRC compared to LSCRC (p = 0.018). Kaplan Meyer survival analysis demonstrated that anti-EGFR antibody therapies were more effective in case of LSCRC compared to RSCRC. Although in case of progression-free survival data just indicated a trend (p = 0.065), in case of overall survival the difference was significant favouring LSCRC (p = 0.047). These data demonstrated for the first time that the EGFR protein expression is significantly higher in KRAS wild type RSLCL as compared to LSCRC. Meanwhile it is somewhat unexpected that the lower EGFR protein expression was found to be associated with better efficacy of anti-EGFR antibody therapies of colorectal cancer, the finding of which must be further validated.