Korean J Gastroenterol.  2010 Jan;55(1):19-25. 10.4166/kjg.2010.55.1.19.

Double Strand Break of DNA in Gastric Adenoma and Adenocarcinoma

• Kim JH
• Kim SS
• Byun SW
• Chang YJ
• Kim JS
• Kim JK
• Cho HJ
• Lim KW
• Jung ES

• KMID: 1775922
• DOI: http://doi.org/10.4166/kjg.2010.55.1.19

Abstract

BACKGROUND/AIMS
DNA double strand break (DSB) is one of the critical types of DNA damage. When unrepaired DSB is accumulated in the nucleus of the cells having mutations in such genes as p53, it will lead to chromosomal instability and further more to mutation of tumor-activating genes resulting in tumorogenesis. Some of malignant cancers and its premalignant lesions were proven to have DSB in their nuclei. The aim of this study was to define the differences in expression of 53BP1 and gamma-H2AX, the markers of DSB, among normal, gastric adenoma, and gastric adenocarcinoma tissues.
METHODS
Tissue microarray was made with the tissues taken from 121 patients who underwent gastrectomy for gastric adenocarcinoma, and 51 patients who underwent endoscopic mucosal resection for gastric adenoma. Immunochemical stain was performed for the marker of DSB, 53BP1 and gamma-H2AX in the tissue microarray. The normal tissues were collected from histologically confirmed tissues with no cellular atypia obtained from the patients with gastric adenocarcinoma.
RESULTS
In gastric carcinoma cells, 53BP1 and gamma-H2AX were highly expressed as compared to normal epithelial cells and gastric adenoma (p<0.01). There were no differences in the expression of 53BP1 and gamma-H2AX between normal epithelium and gastric adenoma. The expression of 53BP1 in the adenoma with grade II and III atypism was more elevated than in those with grade I atypism. The expression of 53BP1 and gamma-H2AX were not significantly different according to the clinicopathologic parameters in the patients with gastric adenocarcinoma.
CONCLUSIONS
The DSB in DNA seems to be associated with the development of gastric adenocarcinoma, but does not affect the premalignant adenoma cells.

Keyword

Gastric adenoma; Gastric adenocarcinoma; DNA double strand break; 53BP1; gamma-H2AX

MeSH Terms

Adenocarcinoma/genetics/*metabolism/secondary
Adenoma/genetics/*metabolism/pathology
Adult
Aged
Aged, 80 and over
Chromosomal Instability
*DNA Breaks, Double-Stranded
Female
Histones/metabolism
Humans
Intracellular Signaling Peptides and Proteins/metabolism
Male
Middle Aged
Neoplasm Staging
Stomach Neoplasms/genetics/*metabolism/pathology

Figure

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  Fig. 1. Visualization of 53BP1 and γ-H2AX expression in normal, adenoma, and gastric adenocarcinoma by immunohistochemistry (×200).

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  Fig. 2. Positive immunostaining of protein 53BP1 and γ-H2AX in normal, adenoma and gastric adenocarcinoma. ∗ Significantly higher compared to normal tissues (p=0.000 in 53BP1, p=0.016 in γ-H2AX).

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