Predictive value and changes of inducible nitric oxide synthase expression in patients with rectal cancer under the influence of antitumor therapy

Abstract

The aim of investigation – to establish the features of iNOS expression in the rectum wall under the influence of various neoadjuvant therapy options in patients with rectal cancer (RC) and to find out its predictive significance. Materials and methods. In 88 patients with stage II–III rectal adenocarcinoma we established iNOS expression in the tumor before and after neoadjuvant radiotherapy (NRT), therapeutic pathomorphosis grade and density of immune cell infiltrates. Patients were divided into 3 groups: 1 – patients after the course of NRT on the tumor site; 2 – patients who underwent chemoradiomodification of the NRT with drug tegafur; 3 – patients who underwent chemoradiomodification of the NRT with tegafur and L-arginine. Results. In the tumors of rectal cancer the level of iNOS expression by 4.5 times exceeded that in the intact rectum wall (P < 0.001), correlated with metastatic lesion of the regional lymph nodes (r = 0.55; P = 0.026) and depended on the type of growth of RC. The level of iNOS expression in the tumor prior to treatment in Group 3 patients, in which the high efficacy of NRT was reported, was 54.61 ± 3.55 versus 35.10 ± 2.28 СU in the rest of the patients (P = 0.01). After NRT, most Groups 1–2 patients reduced the iNOS expression in the RC tissue – on the average to 37.30 ± 4.13 СU, more in the residual parenchyma as compared to the tumor stroma, while Group 1 patients showed the lowest total immunosensitivity intensity of iNOS – 24.34 ± 3.10 CU, and Group 3 patients – the highest – 45.35 ± 5.84 CU. Conclusions. After the use of NRT, iNOS expression in the residual parenchyma of the RC decreased, but in the stroma the marker expression remained unchanged or there was an increase in the marker expression, which was most inherent to therapeutic pathomorphosis grades III–IV. iNOS expression in the RC stroma was highest in patients after NRT with radiomodification using tegafur and L-arginine and positively correlated with the density of immune cell infiltrates in the tumor. Evaluation of the preoperative level of iNOS in patients with RC can serve as a predictive test of advisability of NRT used on the background of radiomodification with L-arginine.