Mitochondrial DNA content and mass increase in progression from normal to hyperplastic to cancer endometrium

Abstract

Background: An increase in mitochondrial DNA (mtDNA) content and mitochondrial biogenesis associated with the activation of PGC-1α signalling pathway was previously reported in type I endometrial cancer. The aim of this study has been to evaluate if mtDNA content and the citrate synthase (CS) activity, an enzyme marker of mitochondrial mass, increase in progression from control endometrium to hyperplasia to type I endometrial carcinoma.

Results: Given that no statistically significant change in mtDNA content and CS activity in endometrium taken from different phases of the menstrual cycle or in menopause was found, these samples were used as control. Our research shows, for the first time, that mtDNA content and citrate synthase activity increase in hyperplastic endometrium compared to control tissues, even if their levels remain lower compared to cancer tissue. In particular, mtDNA content increases seem to precede increases in CS activity. No statistically significant change in mtDNA content and in CS activity was found in relation to different histopathological conditions such as grade, myometrial invasion and stage.

Conclusion: MtDNA content and citrate synthase activity increases in pre-malignant lesions could be a potential molecular marker for progression from hyperplasia to carcinoma.

Figure 1

A) MtDNA content in control, typical hyperplasia, atypical hyperplasia and cancer. MtDNA content has been measured as mtDNA/nDNA ratio. Bars represent the average ± standard deviation of values obtained from different samples analysed in triplicate in 3–4 experiments. n, number of analysed samples. B) Citrate synthase activity in control, typical hyperplasia, atypical hyperplasia and cancer. Measurements of citrate synthase activity (μmoli x min^-1x g tissue^-1) were performed in cellular homogenate. Bars represent the average ± standard deviation of values obtained from different samples analysed in triplicate in 3 different experiments. *p < 0.05 and **p < 0.001 statistically significant differences versus control. § p < 0.05 statistically significant difference versus cancer.