Conflict of Interest: The authors declare that there are no conflicts of interest.
Diagnostic correlation between the expression of the DNA repair enzyme N-methylpurine DNA glycosylase and esophageal adenocarcinoma onset: a retrospective pilot study
Article first published online: 8 NOV 2012
© 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus
Diseases of the Esophagus
Volume 26, Issue 6, pages 644–650, August 2013
How to Cite
Zaïr, Z. M., Johnson, G. E., Griffiths, A. P. and Jenkins, G. J. (2013), Diagnostic correlation between the expression of the DNA repair enzyme N-methylpurine DNA glycosylase and esophageal adenocarcinoma onset: a retrospective pilot study. Diseases of the Esophagus, 26: 644–650. doi: 10.1111/dote.12003
Grant Support: This research was supported by Wales Office of Research and Development for Health and Social Care (grant no. RFS/H09/43) and Hoffman La Roche (grant no. EPBA581607).
- Issue published online: 8 AUG 2013
- Article first published online: 8 NOV 2012
- Wales Office of Research and Development for Health and Social Care. Grant Number: RFS/H09/43
- Hoffman La Roche. Grant Number: EPBA581607
- Barrett's metaplasia;
- base excision repair;
- bile salts;
- esophageal adenocarcinoma;
EAC in its early stages, when it can potentially be cured, is rarely symptomatic and is associated with high mortality rates because in part of late-stage diagnosis. Given that DNA repair is an important contributory factor of early-stage malignancy, our study focused on the expression of the base excision repair enzyme N-methylpurine DNA glycosylase (MPG) in EAC disease onset. MPG messenger RNA (mRNA) expression levels were determined using quantitative reverse transcriptase polymerase chain reaction from a maximum of 72 patient samples. Immunohistochemistry was further utilized for the detection of MPG protein, and semiquantitative analysis performed using an H-score approach was carried out on a total of 130 archival tissue samples of different esophageal pathologies. Nuclear localized MPG protein was detected in all nonmalignant tissues derived from the enterohepatic system, with H-score values of 3.9–5.5 ± 0.4–1.0. In cancerous tissues derived from the enterohepatic system, a 9.5-fold increase in the level of MPG mRNA expression was specifically observed in the malignant regions located within the esophagus region. Further analysis revealed a 9- and 14-fold increase in MPG mRNA expression in EAC tumor, node, metastasis stages II and III, respectively, suggesting MPG expression to correlate with EAC disease progression. Immunohistochemistry analysis further showed a sevenfold significant increase in MPG protein expression in EAC tissues. Intriguingly, there was a fivefold significant decrease in nuclear localized MPG protein expression in tissues derived from Barrett's esophagus and low-grade dysplasia. Such findings highlight a complex regulatory pattern governing DNA glycosylase base excision repair initiation, as normal tissue undergoes Barrett's metaplasia and later dedifferentiates to EAC. Indeed, disease-stage-specific alterations in the expression of MPG may highlight a potential role for MPG in determining EAC onset and thus potentially be of clinical relevance for early disease detection and increased patient survival.