Limits...
Reduced 5-methylcytosine level as a potential progression predictor in patients with T1 or non-invasive urothelial carcinoma.

Chung CJ, Chang CH, Chuu CP, Yang CR, Chang YH, Huang CP, Chen WC, Chung MC, Chang H - Int J Mol Sci (2014)

Bottom Line: Low DNMT1 levels were only associated with UC with squamous differentiation (p = 0.0365).Neither 5-MeC nor DNMT1 levels were associated with UC recurrence.In conclusion, a low 5-MeC level could predict the progression of UC invasion into muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Risk Management, College of Public Health, China Medical University, Taichung 40402, Taiwan. cjchung1010@gmail.com.

ABSTRACT
This study aims to elucidate the level of DNA methylation in urothelial carcinomas (UCs) using 5-methylcytosine (5-MeC) immunohistochemistry (IHC). We examined the relationship among 5-MeC levels, DNA (cytosine-5)-methyltransferase 1 (DNMT1) immunostaining levels, and clinicopathologic features. Tissue samples included 23 normal urothelia and 150 urothelial neoplasia, which comprised 40 non-invasive and 110 invasive UCs. The levels of 5-MeC and DNMT1 were assessed based on their immunoreactivities and then divided into low and high levels. In addition, we collected information on clinical variables, pathologic features, and recurrent status from patient questionnaires and medical records. Chi-square test and multivariate logistic regression model were used for analyses. Results showed that 5-MeC levels were positively associated with DNMT1 levels in UC (p = 0.0288). Both 5-MeC and DNMT1 were low in approximately 50% (76/150) of UC. The percentage of low 5-MeC levels was higher in invasive UC (65/110; 59%) than in normal urothelia (2/23; 13%) and non-invasive UC (18/40; 45%). Clinical factors were independently associated with low 5-MeC levels after adjusting for age and sex, including cancer stages II-IV, presence of UC in situ, and marked inflammation. Low 5-MeC levels in stage I invasive UC were not significantly different from those of non-invasive tumors (p = 0.8478). Low DNMT1 levels were only associated with UC with squamous differentiation (p = 0.0365). Neither 5-MeC nor DNMT1 levels were associated with UC recurrence. In conclusion, a low 5-MeC level could predict the progression of UC invasion into muscle.

Show MeSH

Related in: MedlinePlus

Normal urotheliun. (A) Mouse IgG control; (B) 5-Methylocytosine (5-MeC) immunohistochemistry; (C) DNA (cytosine-5)-methyltransferase 1 (DNMT1) immunohistochemistry. High levels of both 5-MeC and DNMT1 present in the normal urothelium. Bar = 200 µm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4307268&req=5

ijms-16-00677-f001: Normal urotheliun. (A) Mouse IgG control; (B) 5-Methylocytosine (5-MeC) immunohistochemistry; (C) DNA (cytosine-5)-methyltransferase 1 (DNMT1) immunohistochemistry. High levels of both 5-MeC and DNMT1 present in the normal urothelium. Bar = 200 µm.

Mentions: Levels of 5-MeC and DNMT1 for UC are shown in Table 1. The mean basal levels (H-scores) of 5-MeC and DNMT1 in normal urothelia were used as cut-off values (Figure 1); then, a total of UC samples were categorized into low and high levels of 5-MeC or DNMT1 according to H-scores (Figure 2).


Reduced 5-methylcytosine level as a potential progression predictor in patients with T1 or non-invasive urothelial carcinoma.

Chung CJ, Chang CH, Chuu CP, Yang CR, Chang YH, Huang CP, Chen WC, Chung MC, Chang H - Int J Mol Sci (2014)

Normal urotheliun. (A) Mouse IgG control; (B) 5-Methylocytosine (5-MeC) immunohistochemistry; (C) DNA (cytosine-5)-methyltransferase 1 (DNMT1) immunohistochemistry. High levels of both 5-MeC and DNMT1 present in the normal urothelium. Bar = 200 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307268&req=5

ijms-16-00677-f001: Normal urotheliun. (A) Mouse IgG control; (B) 5-Methylocytosine (5-MeC) immunohistochemistry; (C) DNA (cytosine-5)-methyltransferase 1 (DNMT1) immunohistochemistry. High levels of both 5-MeC and DNMT1 present in the normal urothelium. Bar = 200 µm.
Mentions: Levels of 5-MeC and DNMT1 for UC are shown in Table 1. The mean basal levels (H-scores) of 5-MeC and DNMT1 in normal urothelia were used as cut-off values (Figure 1); then, a total of UC samples were categorized into low and high levels of 5-MeC or DNMT1 according to H-scores (Figure 2).

Bottom Line: Low DNMT1 levels were only associated with UC with squamous differentiation (p = 0.0365).Neither 5-MeC nor DNMT1 levels were associated with UC recurrence.In conclusion, a low 5-MeC level could predict the progression of UC invasion into muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Risk Management, College of Public Health, China Medical University, Taichung 40402, Taiwan. cjchung1010@gmail.com.

ABSTRACT
This study aims to elucidate the level of DNA methylation in urothelial carcinomas (UCs) using 5-methylcytosine (5-MeC) immunohistochemistry (IHC). We examined the relationship among 5-MeC levels, DNA (cytosine-5)-methyltransferase 1 (DNMT1) immunostaining levels, and clinicopathologic features. Tissue samples included 23 normal urothelia and 150 urothelial neoplasia, which comprised 40 non-invasive and 110 invasive UCs. The levels of 5-MeC and DNMT1 were assessed based on their immunoreactivities and then divided into low and high levels. In addition, we collected information on clinical variables, pathologic features, and recurrent status from patient questionnaires and medical records. Chi-square test and multivariate logistic regression model were used for analyses. Results showed that 5-MeC levels were positively associated with DNMT1 levels in UC (p = 0.0288). Both 5-MeC and DNMT1 were low in approximately 50% (76/150) of UC. The percentage of low 5-MeC levels was higher in invasive UC (65/110; 59%) than in normal urothelia (2/23; 13%) and non-invasive UC (18/40; 45%). Clinical factors were independently associated with low 5-MeC levels after adjusting for age and sex, including cancer stages II-IV, presence of UC in situ, and marked inflammation. Low 5-MeC levels in stage I invasive UC were not significantly different from those of non-invasive tumors (p = 0.8478). Low DNMT1 levels were only associated with UC with squamous differentiation (p = 0.0365). Neither 5-MeC nor DNMT1 levels were associated with UC recurrence. In conclusion, a low 5-MeC level could predict the progression of UC invasion into muscle.

Show MeSH
Related in: MedlinePlus