PGC1α and VDAC1 expression in endometrial cancer

Abstract

Endometrial cancer (EC) is one of the ten most common gynecological cancers. As in most cancers, EC tumour progression involves alterations in cellular metabolism and can be associated with, for instance, altered levels of glycolytic enzymes. Mitochondrial functions and proteins are known to serve key roles in tumour metabolism and progression. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1α) is a major regulator of mitochondrial biogenesis and function, albeit of varying prognostic value in different cancers. The voltage-dependent anion channel type 1 (VDAC1) regulates apoptosis as well as metabolite import and export over the mitochondrial outer membrane, and is often used for comparative quantification of mitochondrial content. Using immunohistochemistry, the present study examined protein expression levels of PGC1α and VDAC1 in tumour and paired benign tissue samples from 148 patients with EC, in order to examine associations with clinical data, such as stage and grade, Ki-67, p53 status, clinical resistance and overall survival. The expression levels of both PGC1α and VDAC1, as well as a PGC1α downstream effector, were significantly lower in tumor tissues than in benign tissues, suggesting altered mitochondrial function in EC. However, Kaplan-Meier, log rank and Spearman's rank correlation tests revealed that their expression was not correlated with survival and clinical data. Therefore, PGC1α and VDAC1 are not of major prognostic value in EC.

Keywords: coactivator 1; endometrial cancer; mitochondria; peroxisome proliferator-activated receptor γ; prognosis; voltage-dependent anion channel type 1.

Figure 1

Immunohistochemical staining of PGC1α and VDAC1. The images are representative of high and low expression levels, respectively, of PGC1α and VDAC1 in benign and tumour tissue. (A) PGC1α in benign tissue. (B) PGC1α in tumour tissue. (C) VDAC1 in benign tissue. (D) VDAC1 in tumour tissue. Bars indicate 2 mm. PGC1α, peroxisome proliferator-activated receptor γ coactivator 1; VDAC1, voltage-dependent anion channel type 1.

Figure 2

Ki-67 expression. The Ki-67 index, or percentage of tumour cells with a positive nucleus in immunohistochemistry, was significantly higher in tumour cells [31.1 (14.6, 47.9) vs. 1.00 (0.38, 2.60), P<0.0001; Wilcoxon signed rank test]. ^*P<0.05.

Figure 3

PGC1α expression. Immunohistochemical staining and scoring for PGC1α demonstrated significantly lower expression in tumour than in benign tissue [3.0 (3.0, 6.0) vs. 9.00 (6.00, 9.00); P<0.0001; Wilcoxon signed rank test]. Expression levels (y-axis) are based on the proportion of positive cells and the intensity of staining. PGC1α, peroxisome proliferator-activated receptor γ coactivator 1.

Figure 4

VDAC1 expression. Immunohistochemical staining and scoring for VDAC1 demonstrated significantly lower expression in tumour tissues than in benign tissue [6.0 (6.0, 9.0) vs. 9.00 (6.00, 9.00); P=0.005; Wilcoxon signed rank test]. Expression scores (y-axis) are based on the proportion of positive cells and the intensity of staining. VDAC1, voltage-dependent anion channel type 1.