Proteins of the VEGFR and EGFR pathway as predictive markers for adjuvant treatment in patients with stage II/III colorectal cancer: Results of the FOGT-4 trial

Background: unlike metastatic colorectal cancer (crc) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage ii/iii crc patients receiving adjuvant chemotherapy. aim of this study was to assess the predictive value of proteins related with the egfr- and vegfr- signalling cascades in these patients.methods. the patients' data examined in this study were from the collective of the 5-fu/fa versus 5-fu/fa/irinotecan phase iii fogt-4 trial. tumor tissues were stained by immunohistochemistry for vegf-c,vegf-d,vegfr-3,hif-1 pten,areg and ereg expression and evaluated by two independent,blinded investigators. survival analyses were calculated for all patients receiving adjuvant chemotherapy in relation to expression of all makers above.results: patients with negative areg and ereg expression on their tumor had a significant longer dfs in comparison to areg/ereg positive ones (p< 0.05). the benefit on dfs in areg-/ereg- patients was even stronger in the group that received 5-fu/fa/irinotecan as adjuvant treatment (p=0.002). patients with strong expression of pten profited more in terms of os under adjuvant treatment containing irinotecan (p< 0.05). regarding markers of the vegfr- pathway we found no correlation of vegf-c- and vegfr-3 expression with clinical outcome. patients with negative vegf-d expression had a trend to live longer when treated with 5-fu/fa (p=0.106). patients who were negative for hif-1 were disease-free in more than 50% at the end of the study and showed significant longer dfs-rates than those positive for hif-1 p=0.007). this benefit was even stronger at the group treated with 5-fu/fa/irinotecan (p=0.026). finally,areg-/ereg-/pten+ patients showed a trend to live longer under combined treatment combination. -apps conclusions: the addition of irinotecan to adjuvant treatment with 5-fu/fa does not provide os or dfs benefit in patients with stage ii/iii crc. nevertheless,areg/ereg negative,pten positive and hif-1 egative patients might profit significantly in terms of dfs from a treatment containing fluoropyrimidines and irinotecan. our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-fu/fa +/- irinotecan in stage ii/iii colorectal cancer. © 2014 thomaidis et al.; licensee biomed central ltd.