Korean J Gynecol Oncol.  2007 Sep;18(3):201-208.

A study on the expression of p16 gene, methylation of p16 gene promoter and HPV typing in uterine cervical neoplasia

Affiliations
  • 1Department of Obstetrics and Gynecology, College of Medicine, Soonchunhyang Cheonan Hospital, Soonchunhyang University, Cheonan, Korea. dhanbae@schch.co.kr
  • 2Department of Pathology, College of Medicine, Soonchunhyang Cheonan Hospital, Soonchunhyang University, Cheonan, Korea.
  • 3RIC Virus Research Institute, College of Medicine, Soonchunhyang Cheonan Hospital, Soonchunhyang University, Cheonan, Korea.
  • 4Department of Obstetrics and Gynecology, Cheju National University Hospital, Jeju, Korea.

Abstract


OBJECTIVE
p16 is cyclin-dependent kinase (CDK) inhibitor which decelerates cell cycle by inactivating CDKs that phosphorylate retinoblastoma protein (pRb). In cervical carcinogenesis, abnormality of p16 gene such as methylation of p16 gene promoter was investigated as an important factor. The aims of our study are to investigate the expression of p16 gene, methylation of p16 gene promoter region, and HPV typing in uterine cervical neoplasia.
METHODS
A total of 104 samples (CIN1, 30 CIN2,3 45, invasive cancer, 29) were included. Expression of p16 was analyzed by immunohistochemistry, methylation of p16 gene promoter region was analyzed with methylation specific polymerase chain reaction (MSP) and we examed the result of HPV DNA testing.
RESULTS
1. In high risk HPV and low risk or negative group, p16 gene expression was observed in CIN1 (30% vs 23%), CIN2, 3 (64% vs 58%) and in invasive cancer (80% vs 37%) respectively. In invasive cancer, p16 gene expression of high risk HPV group was statistically higher than that of low risk or negative group. 2. In high risk HPV and low risk or negative group, p16 promoter methylation was observed in CIN1 (23% vs 17%), CIN2, 3 (25% vs 47%) and in invasive cancer (19% vs 87%) respectively. In invasive cancer, p16 promoter methylation of low risk or negative HPV group was statistically higher than that of low risk or negative group.
CONCLUSION
p16 gene expression would be marker for CIN and cancer. Methylation of p16 promoter region may be one of the important mechanism for uterine cervical carcinogenesis especially in negative or low risk HPV group. but further studies are needed to reinforce this statement.

Keyword

HPV; DNA methylation; p16 genes; Uterine cervical neoplasms

MeSH Terms

Carcinogenesis
Cell Cycle
DNA Methylation
Genes, p16*
Human Papillomavirus DNA Tests
Immunohistochemistry
Methylation*
Phosphotransferases
Polymerase Chain Reaction
Promoter Regions, Genetic
Retinoblastoma Protein
Uterine Cervical Neoplasms
Phosphotransferases
Retinoblastoma Protein
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