The hypermethylation and protein expression of p16INK4A and DNA repair gene O6 -methylguanine-DNA methyltransferase in various uterine cervical lesions

Zhenhua Lin, Meihua Gao, Xianglan Zhang, Young Sik Kim, Eung Seok Lee, Han Kyeom Kim, Insun Kim

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Purpose: This study is aimed at investigating the significance of gene promoter methylation status and protein expression of p16INK4A and O6-methylguanine-DNA methyltransferase (MGMT) in the various uterine cervical lesions. Materials and methods: Methylation status by using methylation-specific polymerase chain reaction (MS-PCR) and protein expression by using immunohistochemistry for p16INK4A and MGMT genes were performed in cervical squamous intraepithelial neoplasms (CIN), invasive squamous cell carcinomas (SCC), adenocarcinomas and non-neoplastic cervices. Results: None of 20 non-neoplastic cervices showed p16INK4A and MGMT gene hypermethylation, whereas at least one of these genes was hypermethylated with 50.0% (5/10) of CIN I, 65.0% (13/20) of CIN II-III, 70.2% (33/47) of SCC and 85.0% (17/20) of adenocarcinoma. p16INK4A protein was totally negative in non-neoplastic cervices, but positive with 90.0% of CIN I, 100% of CIN II-III and adenocarcinoma, and 78.7% of SCC. MGMT protein was expressed in 10% of non-neoplastic cervices, but significantly increased in SCC (42.5%) and adenocarcinoma (70.0%). The protein expression of p16INK4A and MGMT was not related to their gene promoter methylation status. Conclusions: The hypermethylation of p16INK4A and MGMT genes in the uterine cervix may indicate the presence of malignant cells, and p16INK4A immunostaining is useful in grading CIN and diagnosing invasive SCC and adenocarcinoma.

Original languageEnglish
Pages (from-to)364-370
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Volume131
Issue number6
DOIs
Publication statusPublished - 2005 Jun 1

Fingerprint

Cyclin-Dependent Kinase Inhibitor p16
Cervical Intraepithelial Neoplasia
Methyltransferases
DNA Repair
Cervix Uteri
Squamous Cell Carcinoma
Adenocarcinoma
Methylation
DNA
Genes
Protein Methyltransferases
O-(6)-methylguanine
Immunohistochemistry
Polymerase Chain Reaction

Keywords

  • Cervical uteri
  • Methylation
  • O-methylguanine-DNA methyltransferase
  • p16

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{2de6023adc824d87b3bb22f316d92638,
title = "The hypermethylation and protein expression of p16INK4A and DNA repair gene O6 -methylguanine-DNA methyltransferase in various uterine cervical lesions",
abstract = "Purpose: This study is aimed at investigating the significance of gene promoter methylation status and protein expression of p16INK4A and O6-methylguanine-DNA methyltransferase (MGMT) in the various uterine cervical lesions. Materials and methods: Methylation status by using methylation-specific polymerase chain reaction (MS-PCR) and protein expression by using immunohistochemistry for p16INK4A and MGMT genes were performed in cervical squamous intraepithelial neoplasms (CIN), invasive squamous cell carcinomas (SCC), adenocarcinomas and non-neoplastic cervices. Results: None of 20 non-neoplastic cervices showed p16INK4A and MGMT gene hypermethylation, whereas at least one of these genes was hypermethylated with 50.0{\%} (5/10) of CIN I, 65.0{\%} (13/20) of CIN II-III, 70.2{\%} (33/47) of SCC and 85.0{\%} (17/20) of adenocarcinoma. p16INK4A protein was totally negative in non-neoplastic cervices, but positive with 90.0{\%} of CIN I, 100{\%} of CIN II-III and adenocarcinoma, and 78.7{\%} of SCC. MGMT protein was expressed in 10{\%} of non-neoplastic cervices, but significantly increased in SCC (42.5{\%}) and adenocarcinoma (70.0{\%}). The protein expression of p16INK4A and MGMT was not related to their gene promoter methylation status. Conclusions: The hypermethylation of p16INK4A and MGMT genes in the uterine cervix may indicate the presence of malignant cells, and p16INK4A immunostaining is useful in grading CIN and diagnosing invasive SCC and adenocarcinoma.",
keywords = "Cervical uteri, Methylation, O-methylguanine-DNA methyltransferase, p16",
author = "Zhenhua Lin and Meihua Gao and Xianglan Zhang and Kim, {Young Sik} and Lee, {Eung Seok} and Kim, {Han Kyeom} and Insun Kim",
year = "2005",
month = "6",
day = "1",
doi = "10.1007/s00432-004-0657-5",
language = "English",
volume = "131",
pages = "364--370",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - The hypermethylation and protein expression of p16INK4A and DNA repair gene O6 -methylguanine-DNA methyltransferase in various uterine cervical lesions

AU - Lin, Zhenhua

AU - Gao, Meihua

AU - Zhang, Xianglan

AU - Kim, Young Sik

AU - Lee, Eung Seok

AU - Kim, Han Kyeom

AU - Kim, Insun

PY - 2005/6/1

Y1 - 2005/6/1

N2 - Purpose: This study is aimed at investigating the significance of gene promoter methylation status and protein expression of p16INK4A and O6-methylguanine-DNA methyltransferase (MGMT) in the various uterine cervical lesions. Materials and methods: Methylation status by using methylation-specific polymerase chain reaction (MS-PCR) and protein expression by using immunohistochemistry for p16INK4A and MGMT genes were performed in cervical squamous intraepithelial neoplasms (CIN), invasive squamous cell carcinomas (SCC), adenocarcinomas and non-neoplastic cervices. Results: None of 20 non-neoplastic cervices showed p16INK4A and MGMT gene hypermethylation, whereas at least one of these genes was hypermethylated with 50.0% (5/10) of CIN I, 65.0% (13/20) of CIN II-III, 70.2% (33/47) of SCC and 85.0% (17/20) of adenocarcinoma. p16INK4A protein was totally negative in non-neoplastic cervices, but positive with 90.0% of CIN I, 100% of CIN II-III and adenocarcinoma, and 78.7% of SCC. MGMT protein was expressed in 10% of non-neoplastic cervices, but significantly increased in SCC (42.5%) and adenocarcinoma (70.0%). The protein expression of p16INK4A and MGMT was not related to their gene promoter methylation status. Conclusions: The hypermethylation of p16INK4A and MGMT genes in the uterine cervix may indicate the presence of malignant cells, and p16INK4A immunostaining is useful in grading CIN and diagnosing invasive SCC and adenocarcinoma.

AB - Purpose: This study is aimed at investigating the significance of gene promoter methylation status and protein expression of p16INK4A and O6-methylguanine-DNA methyltransferase (MGMT) in the various uterine cervical lesions. Materials and methods: Methylation status by using methylation-specific polymerase chain reaction (MS-PCR) and protein expression by using immunohistochemistry for p16INK4A and MGMT genes were performed in cervical squamous intraepithelial neoplasms (CIN), invasive squamous cell carcinomas (SCC), adenocarcinomas and non-neoplastic cervices. Results: None of 20 non-neoplastic cervices showed p16INK4A and MGMT gene hypermethylation, whereas at least one of these genes was hypermethylated with 50.0% (5/10) of CIN I, 65.0% (13/20) of CIN II-III, 70.2% (33/47) of SCC and 85.0% (17/20) of adenocarcinoma. p16INK4A protein was totally negative in non-neoplastic cervices, but positive with 90.0% of CIN I, 100% of CIN II-III and adenocarcinoma, and 78.7% of SCC. MGMT protein was expressed in 10% of non-neoplastic cervices, but significantly increased in SCC (42.5%) and adenocarcinoma (70.0%). The protein expression of p16INK4A and MGMT was not related to their gene promoter methylation status. Conclusions: The hypermethylation of p16INK4A and MGMT genes in the uterine cervix may indicate the presence of malignant cells, and p16INK4A immunostaining is useful in grading CIN and diagnosing invasive SCC and adenocarcinoma.

KW - Cervical uteri

KW - Methylation

KW - O-methylguanine-DNA methyltransferase

KW - p16

UR - http://www.scopus.com/inward/record.url?scp=18744385545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18744385545&partnerID=8YFLogxK

U2 - 10.1007/s00432-004-0657-5

DO - 10.1007/s00432-004-0657-5

M3 - Article

C2 - 15785933

AN - SCOPUS:18744385545

VL - 131

SP - 364

EP - 370

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

SN - 0171-5216

IS - 6

ER -