INFLUENCE OF PREOPERATIVE CHEMOTHERAPYON BIOLOGICAL FEATURES OF COLORECTAL CANCER LIVER METASTASES

The modern strategies of chemotherapy of metastatic colorectal cancer (CRC) based on the combination of cytotoxic and targeted angents resulted in significant increase of patient’s life duration. To study the action of anti-EGFR agents (panitumumab), which block the endogenous ligand binding with the receptor, we detected the expression of epidermal growth factor receptor ligands – transforming growth factor α (TGFα) and amphiregulin who take part in CRC progression. To examine the effect of combination of cytotoxic and anti- EGFR agents on adhesive properties of tumor cells the expression of the molecule of intercellular adhesion E-cadherin was investigated. Immunohistochemically there was normal membranous E-cadherin expression in liver metastases of patients who received preoperative chemotherapy (FOLFOX6 in combination with panitumumab) in contrast with pathological membranous and cytoplasmic expression in patients who had no chemotherapy (p=0,002). We demonstrated the lower TGFα and amphiregulin expression in patients who received anti-EGFR therapy compared with control group, but the difference was not statistically reliable. Additionally patients with no chemotherapy and amphiregulin overexpression had higher overall survival than those with low expression (the difference also was not statistically reliable). Our study demonstrated the positive effect of combined cytotoxic and targeted chemotherapy of metastatic colorectal cancer on adhesive properties of tumor cells and inhibition of tumor cell growth by anti-EGFR agents.