Epstein-Barr virus and p16INK4A methylation in squamous cell carcinoma and precancerous lesions of the cervix uteri.
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.
Kim
Na Rae
NR
Department of Pathology, Gachon Medical School Gil Medical Center, Incheon, Korea.
Lin
Zhenhua
Z
Kim
Kyong Rae
KR
Cho
Hyun Yee
HY
Kim
Insun
I
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000235:genetics*; D019175:DNA Methylation; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000473:pathology* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology* / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; C417029:EBV-encoded nuclear antigen 1