Role of thymidylate synthase as a predictor of neoadjuvant chemoradiation therapy in rectal cancer

Abstract

Aim. To study the level of thymidylate synthase gene expression in biopsy material from patients with rectal cancer treated with neoadjuvant chemoradiation therapy. 
 Methods. Analysis of treatment of 101 patients with locally advanced rectal cancer (T3-4, N0-2, M0) was conducted. Measurement of the level of thymidylate synthase gene expression was performed by polymerase chain reaction. To extract ribonucleic acid Qiagen (RNA easy FFPEkit; Qiagen,GmbH,Germany) reagents were used. 
 Results. Cancer pathomorphosis stage TRG 1 was revealed in 23 (22.7%) patients, TRG 2 - in 31 (30.7%) patients, TRG 3 - in 32 (31.7%) patients, complete clinical response (i.e. complete tumor resorption TRG 4) - in 15 (14.9%) patients. Analysis of thymidylate synthase gene expression in patients with poor response to chemoradiation therapy showed that in 34.8% of cases high expression was revealed, while in 65.2% of cases - low expression. Among patients with complete clinical response significant prevalence of patients with high expression of thymidylate synthase gene was revealed - 73.3%, and in 26.7% of patients with pathomorphosis of grade 4 low expression of this gene was registered. In patients with tumor regression grade 2 and 3 no significant difference in patients’ ratio was revealed. The most prominent correlation according to the level of thymidylate synthase gene expression was found in patients without the response to conducted chemoradiation therapy (with prevalence of patients with low expression) and complete tumor regression (with prevalence of patients with high expression). 
 Conclusion. There is inverse correlation between the grade of tumor regression and thymidylate synthase gene expression; evaluation of the level of thymidylate synthase gene expression and response of rectal cancer to neoadjuvant chemoradiation therapy requires further investigation both on molecular and clinical levels.