Epstein-Barr Virus and p16INK4A Methylation in Squamous Cell Carcinoma and Precancerous Lesions of the Cervix Uteri.
10.3346/jkms.2005.20.4.636
- Author:
Na Rae KIM
1
;
Zhenhua LIN
;
Kyong Rae KIM
;
Hyun Yee CHO
;
Insun KIM
Author Information
1. Department of Pathology, Gachon Medical School Gil Medical Center, Incheon, Korea.
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
Protein p16;
Methylation;
Herpesvirus 4, Human;
Epstein-Barr Virus Infections;
Cervix Neoplasms;
Carcinogenesis
- MeSH:
Carcinoma, Squamous Cell/genetics/*pathology/virology;
Comparative Study;
Cyclin-Dependent Kinase Inhibitor p16/analysis/*genetics;
*DNA Methylation;
DNA, Viral/genetics/isolation & purification;
Epstein-Barr Virus Infections/genetics/*pathology/virology;
Epstein-Barr Virus Nuclear Antigens/genetics;
Female;
Herpesvirus 4, Human/genetics;
Humans;
Immunohistochemistry;
In Situ Hybridization;
Polymerase Chain Reaction;
Precancerous Conditions/genetics/*pathology/virology;
RNA, Viral/genetics;
Research Support, Non-U.S. Gov't;
Uterine Cervical Neoplasms/genetics/*pathology/virology
- From:Journal of Korean Medical Science
2005;20(4):636-642
- CountryRepublic of Korea
- Language:English
-
Abstract:
Methylation of p16 is an important mechanism in cervical carcinogenesis. However, the relationship between cervical squamous cell carcinoma (SCC) and Epstein-Barr virus (EBV) remains controversial. Here, we explored whether EBV infection and/or p16 gene inactivation would play any role in cervical carcinogenesis. Eighty-two specimens included 41 invasive SCCs, 30 cervical intraepithelial neoplasm (CIN; CIN 1, 11 cases, CIN II, 3 cases, CIN III 16 cases) and 11 nonneoplastic cervices. EBV was detected by polymerase chain reaction (PCR) for EBNA-1 and in situ hybridization for EBER-1. The p16 methylation-status and the expression of p16 protein were studied by methylation-specific PCR and immunohistochemistry, respectively. The materials were divided into four groups: 1) nonneoplastic cervices, 2) CIN I, 3) CIN II-III and 4) invasive SCCs. p16 methylation and p16 immunoexpressions increased in CIN and invasive SCCs than nonneoplastic tissue. p16-methylation and p16-immunoreactivities were higher in the EBV-positive group (p=0.009, p<0.001) than in the EBV-negative group. EBV was detected more frequently in CIN and SCCs than nonneoplastic cervices. In conclusion, a correlation between p16 methylation, p16 immunoreactivity and the detection of EBV strongly suggested that the cooperation of EBV and p16 gene may play a synergic effect on cell cycle deregulation.
