Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma
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. Tis...
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doaj-f1efdc85c4e544b9885838b9b2fee9822020-11-24T22:19:02ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-12-0116167769010.3390/ijms16010677ijms16010677Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial CarcinomaChi-Jung Chung0Chao-Hsiang Chang1Chih-Pin Chuu2Chi-Rei Yang3Yi-Huei Chang4Chi-Ping Huang5Wen-Chi Chen6Mu-Chi Chung7Han Chang8Department of Health Risk Management, College of Public Health, China Medical University, Taichung 40402, TaiwanDepartment of Urology, China Medical University and Hospital, Taichung 40402, TaiwanInstitute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, TaiwanDepartment of Urology, China Medical University and Hospital, Taichung 40402, TaiwanDepartment of Urology, China Medical University and Hospital, Taichung 40402, TaiwanDepartment of Urology, China Medical University and Hospital, Taichung 40402, TaiwanDepartment of Urology, China Medical University and Hospital, Taichung 40402, TaiwanDivision of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, TaiwanDepartment of Pathology, College of Medicine, China Medical University and Hospital, Taichung 40402, TaiwanThis 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.http://www.mdpi.com/1422-0067/16/1/6775-methylcytosineimmunohistochemistryurothelial carcinomaDNA (cytosine-5)-methyltransferase 1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chi-Jung Chung Chao-Hsiang Chang Chih-Pin Chuu Chi-Rei Yang Yi-Huei Chang Chi-Ping Huang Wen-Chi Chen Mu-Chi Chung Han Chang |
spellingShingle |
Chi-Jung Chung Chao-Hsiang Chang Chih-Pin Chuu Chi-Rei Yang Yi-Huei Chang Chi-Ping Huang Wen-Chi Chen Mu-Chi Chung Han Chang Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma International Journal of Molecular Sciences 5-methylcytosine immunohistochemistry urothelial carcinoma DNA (cytosine-5)-methyltransferase 1 |
author_facet |
Chi-Jung Chung Chao-Hsiang Chang Chih-Pin Chuu Chi-Rei Yang Yi-Huei Chang Chi-Ping Huang Wen-Chi Chen Mu-Chi Chung Han Chang |
author_sort |
Chi-Jung Chung |
title |
Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma |
title_short |
Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma |
title_full |
Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma |
title_fullStr |
Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma |
title_full_unstemmed |
Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma |
title_sort |
reduced 5-methylcytosine level as a potential progression predictor in patients with t1 or non-invasive urothelial carcinoma |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2014-12-01 |
description |
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. |
topic |
5-methylcytosine immunohistochemistry urothelial carcinoma DNA (cytosine-5)-methyltransferase 1 |
url |
http://www.mdpi.com/1422-0067/16/1/677 |
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