Loss expression of O6-methylguanine DNA methyltransferase by promoter hypermethylation and its relationship to betel quid chewing in oral squamous cell carcinoma.
OBJECTIVE
O(6)-methylguanine-DNA methyltransferase (MGMT) ameliorates mutagenic, carcinogenic, and cytotoxic adducts from O(6)-methylguanine in DNA through a direct reversal mechanism. Decreased expression of MGMT has been reported in a variety of human malignant tumors. The purpose of this study was to clarify the correlation of MGMT expression levels in oral squamous cell carcinoma (OSCC) with promoter hypermethylation and with betel quid chewing and cigarette smoking.


METHODS
MGMT protein expression in 63 cases of oral squamous cell carcinoma by immunohistochemistry was investigated. Methylation status of the MGMT was analyzed by methylation-specific PCR. Correlation with clinicopathologic parameters was then tested by statistical analysis.


RESULTS
MGMT immunohistochemistry revealed nuclear staining in normal epithelium, whereas 47 (75%) of 63 OSCC tumors were devoid of MGMT expression and this was related to tumor cell differentiation. Furthermore, the association between loss of MGMT expression and promoter hypermethylation was significant. Lacking protein expression for MGMT in OSCC was also associated with the use of betel quid.


CONCLUSIONS
The results suggest that the absence of MGMT expression, which would seem to be associated with promoter hypermethylation, is related to betel quid chewing and, thus, in turn, might be a significant event in oral carcinogenesis.
Huang
Sung-Hsien
SH
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Lee
Herng-Sheng
HS
Mar
Kwei
K
Ji
Dar-Der
DD
Huang
Mao-Suan
MS
Hsia
Kan-Tai
KT
D000328:Adult; D001114:Areca / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects; D018709:Statistics, Nonparametric
D019853:O(6)-Methylguanine-DNA Methyltransferase