INFLUENCE OF CYTOTOXIC CHEMOTHERAPY ON THE ERCC1, XPD AND DPYD EXPRESSION IN COLORECTAL CANCER LIVER METASTASES

DOI: https://doi.org/None

E.M. Paltseva (1), A.V. Varlamov (1,2), M.I. Sekacheva (1), D.N. Fedorov (1), O.G. Skipenko (1) 1 -B.V. Petrovsky Russian Surgery Research Center, Abrikosovskiy per., 2, Moscow, 119991, Russian Federation 2 -Research Institute of Human Morphology, Tsyurupy per., 3, Moscow, 117418, Russian Federation

Introduction. The elevated expression of components of DNA repair system ERCC1 (excision repair cross-complementing group 1) and XPD (Xeroderma pigmentosum group D) is associated with the lack of efficacy of DNA–damaging cytotoxic platinum-based preparations. The key enzyme in a catabolism of 5-fluorouracil, included in the standard schemes of this therapy, is dihydropyrimidine dehydrogenase (DPYD), which also has the influence on the susceptibility of tumor cells to the treatment. The aim of this research was the study of ERCC1, XPD and DPYD expression in metastatic lesions of colorectal cancer (CRC) in patients who received preoperative cytotoxic chemotherapy. Methods. Immunohistochemical examination was performed on the surgical samples of 105 CRC patients with liver metastases. There was made an evaluation of drug pathomorphosis in 53 patients who received the cytotoxic therapy. The comparison group was consisted of 52 patients without the preoperative drug treatment. Results. The cytotoxic drugs significantly decreased the DNA repair activity in tumor cells by suppressing the expression of one of the components of the NER system – nuclease ERCC1 (p=0,01), but didn’t influence on the expression level of another component – XPD protein (p=0,2). When comparing the results of the investigation of DPYD we found neither significant differences between groups nor associations with the extent of pathomorphosis, but this enzyme wasn’t detected in the majority of cases. Drug pathomorphosis of the degrees II and III occurred most frequently.Conclusion. In our investigation cytotoxic therapy was shown to diminish the DNA repair activity in tumor cells by virtue of the suppressing of ERCC1 expression. The revealed low content of enzyme DPYD gives reason to suggest the good efficacy of 5-fluorouracil in relation to metastatic CRC.
Keywords: 
metastatic colorectal cancer, cytotoxic therapy, drug pathomorphosis, ERCC1, XPD, DPYD
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