IMMUNOHISTOCHEMICAL AND GENETIC PROGNOSTIC FACTORS OF NEOADJUVANT CHEMORADIOTHERAPY EFFICАCY IN PERSONALIZED TREATMENT OF LOCAL ADVANCED RECTAL CANCER

Abstract

The aim: The aim of our study was to define the factors that can robustly predict a response to neoadjuvant chemoradiotherapy (NCRT) in patients with local advanced rectal cancer (LARC) and prognosis factors of progression free survival (PFS) using molecular (8-oxodGu), immunohystochemical (Ki-67) and genetic (GSTP1 and MTHFR genes polymorphism) markers. Materials and methods: GSTP1 and MTHFR polymorphisms were studied by real-time PCR on tumour material from 110 patients with LARC. Ki-67 protein expression was assessed using rabbit monoclonal antibodies to Ki-67 (Dako, Denmark) on EnVisionTM FLEX detection system (Dako, Denmark). 8-oxodGu level in eluate was measured by spectrophotometry. Results: Patients from both groups showed significant pathomorphological response to NCRT. It is robust correlation between 8-oxodGu levels in patients’ blood and their response to CRT (mrTRG scale) in MG was determined. Oxaliplatin-containing chemotherapy promotes statistically significant decrease of 8-oxodGu levels. With the decrease of Ki-67 protein expression level the probability of tumour relapse increases. It is determined that critical value of Ki-67 protein expression level makes less than 27 and tumour relapse probability in this case makes 50%. Tumour relapse risk in patients with GSTP1 and MTHFR polymorphism is 12.3 and 16.3 times higher than in patients who do not carry such polymorphism, respectively. Combination of GSTP1, МTНFR polymorphisms and Кі-67 protein expression factors determines prognostic probability of tumour relapse within 51-99%. Conclusions: 8-oxodGu level can serve as independent prognostic factor of NCRT efficacy in patients with LARC. Combination of GSTP1, МTНFR genes polymorphism with Кі-67 protein expression decrease enables monitoring and robust prognosis of LARC relapse.