TY - JOUR
T1 - Loss expression of O6-methylguanine DNA methyltransferase by promoter hypermethylation and its relationship to betel quid chewing in oral squamous cell carcinoma
AU - Huang, Sung Hsien
AU - Lee, Herng Sheng
AU - Mar, Kwei
AU - Ji, Dar Der
AU - Huang, Mao Suan
AU - Hsia, Kan Tai
PY - 2010
Y1 - 2010
N2 - Objective: O6-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. Study design: 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.
AB - Objective: O6-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. Study design: 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.
UR - http://www.scopus.com/inward/record.url?scp=77955294819&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955294819&partnerID=8YFLogxK
U2 - 10.1016/j.tripleo.2009.12.019
DO - 10.1016/j.tripleo.2009.12.019
M3 - Article
C2 - 20451846
AN - SCOPUS:77955294819
SN - 1079-2104
VL - 109
SP - 883
EP - 889
JO - Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology
JF - Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology
IS - 6
ER -