The hypermethylation and protein expression of p16 INK4A and DNA repair gene O6-methylguanine-DNA methyltransferase in various uterine cervical lesions.
OBJECTIVE
This study is aimed at investigating the significance of gene promoter methylation status and protein expression of p16 INK4A and O6-methylguanine-DNA methyltransferase (MGMT) in the various uterine cervical lesions.


METHODS
Methylation status by using methylation-specific polymerase chain reaction (MS-PCR) and protein expression by using immunohistochemistry for p16 INK4A 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 p16 INK4A 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. p16 INK4A 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 p16 INK4A and MGMT was not related to their gene promoter methylation status.


CONCLUSIONS
The hypermethylation of p16 INK4A and MGMT genes in the uterine cervix may indicate the presence of malignant cells, and p16 INK4A immunostaining is useful in grading CIN and diagnosing invasive SCC and adenocarcinoma.
Lin
Zhenhua
Z
Department of Pathology, Korea University College of Medicine, Seoul, South Korea.
Gao
Meihua
M
Zhang
Xianglan
X
Kim
Young-Sik
YS
Lee
Eung-Seok
ES
Kim
Han-Kyeom
HK
Kim
Insun
I
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002584:Cervix Uteri / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D004260:DNA Repair; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA; D019853:O(6)-Methylguanine-DNA Methyltransferase