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Differential LINE-1 Hypomethylation of Gastric Low-Grade Dysplasia from High Grade Dysplasia and Intramucosal Cancer.

Lee JR, Chung WC, Kim JD, Lee KM, Paik CN, Jung SH, Jung JH, Lee YK, Han SW - Gut Liver (2011)

Bottom Line: A total of 145 tissue samples were analyzed by two histopathologists.A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used.Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88).

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea.

ABSTRACT

Background/aims: Gastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer.

Methods: A total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used.

Results: Gastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88).

Conclusions: LINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer.

No MeSH data available.


Related in: MedlinePlus

LINE-1 hypomethylation levels in gastric epithelial dysplasia and intramucosal cancer. When compared to adjacent normal mucosa, gastric epithelial dysplasia and cancer tissues have significantly lower LINE-1 methylation levels. Box plots illustrate median values, 25th and 75th percentiles, and outliers on a linear scale. The unpaired t-test is applied for nonparametric statistical analysis, and a p value of less than 0.05 is considered significant.N, normal; T, tumor.
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Figure 2: LINE-1 hypomethylation levels in gastric epithelial dysplasia and intramucosal cancer. When compared to adjacent normal mucosa, gastric epithelial dysplasia and cancer tissues have significantly lower LINE-1 methylation levels. Box plots illustrate median values, 25th and 75th percentiles, and outliers on a linear scale. The unpaired t-test is applied for nonparametric statistical analysis, and a p value of less than 0.05 is considered significant.N, normal; T, tumor.

Mentions: The level of LINE-1 methylation in the gastric epithelial lesions and adjacent normal mucosa, from the same subject, was examined by a modified COBRA LINE-1 method (Fig. 1). The gastric epithelial dysplasia and cancer tissues had significantly lower levels of LINE-1 methylation than the adjacent normal tissues (Fig. 2). In gastric epithelial dysplasia, the dysplasia lesion showed a significantly lower LINE-1 methylation level (42.85±0.63%) compared to normal epithelium (46.35±0.69%) (p<0.01). In intramucosal cancer, the cancer lesion showed a significantly lower LINE-1 methylation level (40.23±0.92%) compared to normal epithelium (45.94±1.78%) (p<0.01). When the dysplastic lesions with H. pylori infection compared to the lesions without infection, there was no significant difference (42.46±0.88 and 43.22±0.89, p=0.27).


Differential LINE-1 Hypomethylation of Gastric Low-Grade Dysplasia from High Grade Dysplasia and Intramucosal Cancer.

Lee JR, Chung WC, Kim JD, Lee KM, Paik CN, Jung SH, Jung JH, Lee YK, Han SW - Gut Liver (2011)

LINE-1 hypomethylation levels in gastric epithelial dysplasia and intramucosal cancer. When compared to adjacent normal mucosa, gastric epithelial dysplasia and cancer tissues have significantly lower LINE-1 methylation levels. Box plots illustrate median values, 25th and 75th percentiles, and outliers on a linear scale. The unpaired t-test is applied for nonparametric statistical analysis, and a p value of less than 0.05 is considered significant.N, normal; T, tumor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3140658&req=5

Figure 2: LINE-1 hypomethylation levels in gastric epithelial dysplasia and intramucosal cancer. When compared to adjacent normal mucosa, gastric epithelial dysplasia and cancer tissues have significantly lower LINE-1 methylation levels. Box plots illustrate median values, 25th and 75th percentiles, and outliers on a linear scale. The unpaired t-test is applied for nonparametric statistical analysis, and a p value of less than 0.05 is considered significant.N, normal; T, tumor.
Mentions: The level of LINE-1 methylation in the gastric epithelial lesions and adjacent normal mucosa, from the same subject, was examined by a modified COBRA LINE-1 method (Fig. 1). The gastric epithelial dysplasia and cancer tissues had significantly lower levels of LINE-1 methylation than the adjacent normal tissues (Fig. 2). In gastric epithelial dysplasia, the dysplasia lesion showed a significantly lower LINE-1 methylation level (42.85±0.63%) compared to normal epithelium (46.35±0.69%) (p<0.01). In intramucosal cancer, the cancer lesion showed a significantly lower LINE-1 methylation level (40.23±0.92%) compared to normal epithelium (45.94±1.78%) (p<0.01). When the dysplastic lesions with H. pylori infection compared to the lesions without infection, there was no significant difference (42.46±0.88 and 43.22±0.89, p=0.27).

Bottom Line: A total of 145 tissue samples were analyzed by two histopathologists.A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used.Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88).

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea.

ABSTRACT

Background/aims: Gastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer.

Methods: A total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used.

Results: Gastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88).

Conclusions: LINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer.

No MeSH data available.


Related in: MedlinePlus