title: Reduced 5-methylcytosine level as a potential progression predictor in patients with T1 or non-invasive urothelial carcinoma.
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.
authors.affiliation: Department of Health Risk Management, College of Public Health, China Medical University, Taichung 40402, Taiwan. cjchung1010@gmail.com.
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Chung
authors.affiliation: Department of Urology, China Medical University and Hospital, Taichung 40402, Taiwan. d8395@mail.cmuh.org.tw.
authors.forename: Chao-Hsiang
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. cpchuu@nhri.org.tw.
authors.forename: Chih-Pin
authors.initials: CP
authors.lastname: Chuu
authors.affiliation: Department of Urology, China Medical University and Hospital, Taichung 40402, Taiwan. cryang@mail.cmuh.org.tw.
authors.forename: Chi-Rei
authors.initials: CR
authors.lastname: Yang
authors.affiliation: Department of Urology, China Medical University and Hospital, Taichung 40402, Taiwan. D21959@mail.cmuh.org.tw.
authors.forename: Yi-Huei
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Department of Urology, China Medical University and Hospital, Taichung 40402, Taiwan. d17561@mail.cmuh.org.tw.
authors.forename: Chi-Ping
authors.initials: CP
authors.lastname: Huang
authors.affiliation: Department of Urology, China Medical University and Hospital, Taichung 40402, Taiwan. wgchen@mail.cmu.edu.tw.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan. mcchung0322@gmail.com.
authors.forename: Mu-Chi
authors.initials: MC
authors.lastname: Chung
authors.affiliation: Department of Pathology, College of Medicine, China Medical University and Hospital, Taichung 40402, Taiwan. changhan@mail.cmu.edu.tw.
authors.forename: Han
authors.initials: H
authors.lastname: Chang
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D014571:Urologic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D044503:5-Methylcytosine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human