Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ

Yohei Horikawa, Kokichi Sugano, Masanori Shigyo, Hidenobu Yamamoto, Masaaki Nakazono, Hiroyuki Fujimoto, Yae Kanai, Setsuo Hirohashi, Tadao Kakizoe, Tomonori Habuchi, Tetsuro Kato

Research output: Contribution to journalArticle

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Abstract

Purpose: We elucidated the role of methylation in the promoter region of the CDH1 gene in bladder carcinogenesis, particularly in those comprising carcinoma in situ. Materials and Methods: A total of 49 cases of transitional cell carcinoma of the bladder obtained from transurethral resection were examined. Methylation status of the CDH1 promoter region was analyzed by methylation specific polymerase chain reaction from chemically modified DNA after Na-bisulfite treatment. Loss of heterozygosity on 16q was examined by blunt end single strand DNA conformation polymorphism using 4 tetranucleotide repeat microsatellite markers assigned on 16q13 to 22.1. E-cadherin expression was evaluated by immunostaining on formalin fixed, paraffin embedded tissue sections using anti E-cadherin murine monoclonal antibody, HECD1 and standard avidin-biotin immunoperoxidase complex technique. Results: Analysis of the 49 bladder transitional cell carcinoma samples showed CDH1 promoter methylation in 23 (47%). Methylation of the CDH1 gene did not correlate with tumor stage (p = 0.2097) but with high grade transitional cell carcinoma (p = 0.0416). CDH1 promoter methylation was observed at a significantly higher frequency in the carcinoma in situ positive group than in the carcinoma in situ negative group (16 of 18 cases or 89% versus 7 of 31 or 23%, p <0.0001) and it strongly correlated with abnormal E-cadherin expression (p <0.0001). We found 16q loss of heterozygosity in 16 of 47 cases (34%), which correlated with higher histological grade (p = 0.0069) but not with the presence of the carcinoma in situ component (p = 0.1235). Conclusions: This study showed that CDH1 gene promoter methylation is strongly associated with bladder transitional cell carcinoma comprising carcinoma in situ.

Original languageEnglish
Pages (from-to)1541-1545
Number of pages5
JournalJournal of Urology
Volume169
Issue number4
DOIs
Publication statusPublished - 2003 Apr 1
Externally publishedYes

Fingerprint

Transitional Cell Carcinoma
Carcinoma in Situ
Cadherins
Genetic Promoter Regions
Methylation
Urinary Bladder
Loss of Heterozygosity
Microsatellite Repeats
Genes
Nucleic Acid Conformation
Avidin
Biotin
Immunoenzyme Techniques
Paraffin
Formaldehyde
Carcinogenesis
Monoclonal Antibodies
Polymerase Chain Reaction
DNA
Neoplasms

Keywords

  • Bladder
  • Cadherins
  • Carcinoma
  • Carcinoma in situ
  • Gene expression
  • Transitional cell

ASJC Scopus subject areas

  • Urology

Cite this

Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ. / Horikawa, Yohei; Sugano, Kokichi; Shigyo, Masanori; Yamamoto, Hidenobu; Nakazono, Masaaki; Fujimoto, Hiroyuki; Kanai, Yae; Hirohashi, Setsuo; Kakizoe, Tadao; Habuchi, Tomonori; Kato, Tetsuro.

In: Journal of Urology, Vol. 169, No. 4, 01.04.2003, p. 1541-1545.

Research output: Contribution to journalArticle

Horikawa, Y, Sugano, K, Shigyo, M, Yamamoto, H, Nakazono, M, Fujimoto, H, Kanai, Y, Hirohashi, S, Kakizoe, T, Habuchi, T & Kato, T 2003, 'Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ', Journal of Urology, vol. 169, no. 4, pp. 1541-1545. https://doi.org/10.1097/01.ju.0000046242.55722.1c
Horikawa, Yohei ; Sugano, Kokichi ; Shigyo, Masanori ; Yamamoto, Hidenobu ; Nakazono, Masaaki ; Fujimoto, Hiroyuki ; Kanai, Yae ; Hirohashi, Setsuo ; Kakizoe, Tadao ; Habuchi, Tomonori ; Kato, Tetsuro. / Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ. In: Journal of Urology. 2003 ; Vol. 169, No. 4. pp. 1541-1545.
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abstract = "Purpose: We elucidated the role of methylation in the promoter region of the CDH1 gene in bladder carcinogenesis, particularly in those comprising carcinoma in situ. Materials and Methods: A total of 49 cases of transitional cell carcinoma of the bladder obtained from transurethral resection were examined. Methylation status of the CDH1 promoter region was analyzed by methylation specific polymerase chain reaction from chemically modified DNA after Na-bisulfite treatment. Loss of heterozygosity on 16q was examined by blunt end single strand DNA conformation polymorphism using 4 tetranucleotide repeat microsatellite markers assigned on 16q13 to 22.1. E-cadherin expression was evaluated by immunostaining on formalin fixed, paraffin embedded tissue sections using anti E-cadherin murine monoclonal antibody, HECD1 and standard avidin-biotin immunoperoxidase complex technique. Results: Analysis of the 49 bladder transitional cell carcinoma samples showed CDH1 promoter methylation in 23 (47{\%}). Methylation of the CDH1 gene did not correlate with tumor stage (p = 0.2097) but with high grade transitional cell carcinoma (p = 0.0416). CDH1 promoter methylation was observed at a significantly higher frequency in the carcinoma in situ positive group than in the carcinoma in situ negative group (16 of 18 cases or 89{\%} versus 7 of 31 or 23{\%}, p <0.0001) and it strongly correlated with abnormal E-cadherin expression (p <0.0001). We found 16q loss of heterozygosity in 16 of 47 cases (34{\%}), which correlated with higher histological grade (p = 0.0069) but not with the presence of the carcinoma in situ component (p = 0.1235). Conclusions: This study showed that CDH1 gene promoter methylation is strongly associated with bladder transitional cell carcinoma comprising carcinoma in situ.",
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T1 - Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ

AU - Horikawa, Yohei

AU - Sugano, Kokichi

AU - Shigyo, Masanori

AU - Yamamoto, Hidenobu

AU - Nakazono, Masaaki

AU - Fujimoto, Hiroyuki

AU - Kanai, Yae

AU - Hirohashi, Setsuo

AU - Kakizoe, Tadao

AU - Habuchi, Tomonori

AU - Kato, Tetsuro

PY - 2003/4/1

Y1 - 2003/4/1

N2 - Purpose: We elucidated the role of methylation in the promoter region of the CDH1 gene in bladder carcinogenesis, particularly in those comprising carcinoma in situ. Materials and Methods: A total of 49 cases of transitional cell carcinoma of the bladder obtained from transurethral resection were examined. Methylation status of the CDH1 promoter region was analyzed by methylation specific polymerase chain reaction from chemically modified DNA after Na-bisulfite treatment. Loss of heterozygosity on 16q was examined by blunt end single strand DNA conformation polymorphism using 4 tetranucleotide repeat microsatellite markers assigned on 16q13 to 22.1. E-cadherin expression was evaluated by immunostaining on formalin fixed, paraffin embedded tissue sections using anti E-cadherin murine monoclonal antibody, HECD1 and standard avidin-biotin immunoperoxidase complex technique. Results: Analysis of the 49 bladder transitional cell carcinoma samples showed CDH1 promoter methylation in 23 (47%). Methylation of the CDH1 gene did not correlate with tumor stage (p = 0.2097) but with high grade transitional cell carcinoma (p = 0.0416). CDH1 promoter methylation was observed at a significantly higher frequency in the carcinoma in situ positive group than in the carcinoma in situ negative group (16 of 18 cases or 89% versus 7 of 31 or 23%, p <0.0001) and it strongly correlated with abnormal E-cadherin expression (p <0.0001). We found 16q loss of heterozygosity in 16 of 47 cases (34%), which correlated with higher histological grade (p = 0.0069) but not with the presence of the carcinoma in situ component (p = 0.1235). Conclusions: This study showed that CDH1 gene promoter methylation is strongly associated with bladder transitional cell carcinoma comprising carcinoma in situ.

AB - Purpose: We elucidated the role of methylation in the promoter region of the CDH1 gene in bladder carcinogenesis, particularly in those comprising carcinoma in situ. Materials and Methods: A total of 49 cases of transitional cell carcinoma of the bladder obtained from transurethral resection were examined. Methylation status of the CDH1 promoter region was analyzed by methylation specific polymerase chain reaction from chemically modified DNA after Na-bisulfite treatment. Loss of heterozygosity on 16q was examined by blunt end single strand DNA conformation polymorphism using 4 tetranucleotide repeat microsatellite markers assigned on 16q13 to 22.1. E-cadherin expression was evaluated by immunostaining on formalin fixed, paraffin embedded tissue sections using anti E-cadherin murine monoclonal antibody, HECD1 and standard avidin-biotin immunoperoxidase complex technique. Results: Analysis of the 49 bladder transitional cell carcinoma samples showed CDH1 promoter methylation in 23 (47%). Methylation of the CDH1 gene did not correlate with tumor stage (p = 0.2097) but with high grade transitional cell carcinoma (p = 0.0416). CDH1 promoter methylation was observed at a significantly higher frequency in the carcinoma in situ positive group than in the carcinoma in situ negative group (16 of 18 cases or 89% versus 7 of 31 or 23%, p <0.0001) and it strongly correlated with abnormal E-cadherin expression (p <0.0001). We found 16q loss of heterozygosity in 16 of 47 cases (34%), which correlated with higher histological grade (p = 0.0069) but not with the presence of the carcinoma in situ component (p = 0.1235). Conclusions: This study showed that CDH1 gene promoter methylation is strongly associated with bladder transitional cell carcinoma comprising carcinoma in situ.

KW - Bladder

KW - Cadherins

KW - Carcinoma

KW - Carcinoma in situ

KW - Gene expression

KW - Transitional cell

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