Redox status of endometrial tumors: A comparative study in endometrioid adenocarcinoma, serous, and clear cell carcinomas.

Abstract

e17619 Background: Oxidative stress, reflecting an imbalance between the formation of reactive oxygen species and the body's antioxidant defenses, plays a key role in cancer development and progression. However, in endometrial cancer (EC), the leading oncogynecological malignancy, the characteristics of redox status across different histological types have not been sufficiently studied. The purpose of this study was to investigate the levels of lipid peroxidation (LPO) products, the activity of antioxidant enzymes, and the non-enzymatic components of the antioxidant system in tumors of different EC types. Methods: Levels of diene conjugates (DC) and malondialdehyde (MDA), activity of superoxide dismutase (SOD), catalase (CT), glutathione peroxidase (GPO), glutathione-S-transferase (GT), and contents of reduced glutathione (RG) and vitamins A and E were measured in tumor tissues of patients with endometrioid adenocarcinoma G3 (AC, n=15), clear cell endometrial carcinoma (CCE, n=11), and serous endometrial cancer (SEC, n=12) using standard biochemical methods. Parameters from intact uterine tissue of patients with myoma (n=8) served as the comparison group. Statistical analysis was performed with the Statistics 10.0 program. Results: The level of primary LPO products (DC) was increased in AC G3 by 2.9-fold (p=0.02), and in CCE and SEC by 4.0-fold and 3.5-fold, respectively (p<0.0005), compared with intact uterine tissue. The content of MDA was most elevated in AC G3 tumors — by 1.6-fold (p=0.001). The activity of first-line antioxidant enzymes was highest in CCE: SOD increased 8.3-fold and CT 11.3-fold; in SEC, the increases were 6.6-fold and 6.7-fold; in AC G3, 5.9-fold and 3.0-fold, respectively (p≤0.0003). An imbalance in the functioning of these enzymes was observed: in AC, SOD predominated by 2-fold, whereas in CCE and SEC, CT predominated by 1.4–1.5-fold. CCE was characterized by the highest activity of GT and GPO alongside an almost 3-fold decrease in RG. Conversely, in SEC, a 2-fold decrease in GPO activity, a 4-fold decrease in GT activity, and a 5-fold decrease in the levels of both vitamins were observed. Conclusions: In all types of endometrial cancer, activation of SOD and CT plays a key role in the antioxidant defense of tumor cells. In clear cell endometrial carcinoma, the glutathione system also contributes to protecting tumor cells from oxidative stress, potentially promoting aggressive growth and rapid invasion. The pronounced inhibition of glutathione-dependent enzymes and the marked reduction in vitamin levels in serous endometrial cancer may contribute to the formation of a mutated p53 protein, which is associated with aggressiveness and poor prognosis in this histological subtype.