Expression and prognostic significance of human peroxiredoxin isoforms in endometrial cancer

Abstract

Endometrial cancer is a common type of malignant tumor of the human female genital tract, which typically occurs after menopause. Asian nations, including Korea, Japan and China, have a 4-5 times lower incidence than Western industrialized nations. However, in recent years, there has been a marked increase in the incidence of the disease. Peroxiredoxin (Prx) is an antioxidant enzyme that consists of six isoforms in mammals. These enzymes share a common reactive Cys residue in the N-terminal region, and are capable of breaking down H(2)O(2) as a peroxidase and involving thioredoxin or glutathione as the electron donor. In the present study, we evaluated the expression of Prx isoforms in normal endometrium, endometrial hyperplasia and endometrial cancer. A total of 240 patients, diagnosed with endometrial cancer by immunohistochemistry, were enrolled in this study. Results showed that Prx I, III, IV and V were negative or weakly expressed in normal endometrium, whereas levels of Prx II and VI were strongly expressed. Notably, the expression levels of Prx III and V were upregulated in endometrial cancer, compared with normal endometrium and endometrial hyperplasia. However, no differences in the staining intensities according to the grade of lesion were observed in the other Prx isoforms. The Kaplan-Meier survival analysis demonstrated that Prx V expression in endometrial cancer is significantly associated with survival rate. Therefore, we suggest that Prx V is a clinically significant prognostic marker for the development of endometrial cancer.

Figure 1

Immunohistochemical staining of Prx isoforms in human endometrial tissues. (A) Prx I, (B) Prx II, (C) Prx III, (D) Prx IV, (E) Prx V and (F) Prx VI. Each Prx isoform (A, B, C, D, E and F) was immunostained in (N) normal endometrium, (H) endometrial hyperplasia and (C) endometrial cancer samples. Prx, peroxiredoxin.

Figure 2

Immunohistochemical staining results of the peroxiredoxin isoforms in human endometrial tissues. Distribution of the Prx I, II, III, IV, V and IV expression in each histopathological group of normal endometrium (normal), endometrial hyperplasia (hyper) and endometrial cancer (cancer) tissues are shown as: intensity +++, intensity ++, intensity + and negative. The immunostaining of Prx III and Prx V were significantly increased during endometrial cancer progression. (p≤0.05). Prx, peroxiredoxin.

Figure 3

Kaplan-Meier survival curve for endometrial cancer patients based on the expression of Prx V. Patients were followed-up for a period of 96 months after surgery. High Prx V expression is significantly associated with lower cumulative survival rates (P=0.006). The log-rank test was used to compare the difference in survival times between the high and low Prx V expression groups.