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

Antonella Cormio,Giuseppe Putignano,Vito Pesce,Luigi Eustacchio Selvaggi,Vera Loizzi,Flora Guerra,Palmiro Cantatore,Flavio Fracasso,Leonardo Resta,Gennaro Cormio,Maria Nicola Gadaleta

doi:10.1186/1756-0500-5-279

Abstract

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

Highlights

An increase in mitochondrial DNA content and mitochondrial biogenesis associated with the activation of PGC-1α signalling pathway was previously reported in type I endometrial cancer
Analysis of mitochondrial DNA (mtDNA) content in control, hyperplastic and cancer endometrial tissues MtDNA content relative to nuclear DNA content in 16 proliferative, 7 secretive and 9 atrophic endometria was measured by real-time PCR
In typical and atypical hyperplasia, citrate synthase (CS) activity is significantly lower compared to cancer tissue samples

Summary

Introduction

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. The development of endometrioid cancer is usually considered a multistep process with slow progression from normal endometrium to hyperplasia to cancer as a result of excesses in endogenous or exogenous estrogens and/or relative progesterone deficiency [2]. Endometrial hyperplasia may be associated with cytologic atypia (atypical hyperplasia). About 22% of patients with atypical hyperplasia can develop cancer [4]

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Conclusion