The correlation and prognostic significance of MGMT promoter methylation and MGMT protein in glioblastomas.
OBJECTIVE
The aim of this study was to evaluate the correlation and prognostic significance of MGMT promoter methylation and protein expression in patients with glioblastoma.


METHODS
Eighty-three patients with glioblastoma underwent surgery followed by radiotherapy and temozolomide chemotherapy between October 2000 and June 2008. To investigate the correlation between MGMT methylation and MGMT expression, methylation-specific polymerase chain reaction (MSP) and immunohistochemical staining was performed. To analyze the correlation between MGMT methylation and MGMT expression according to location, biopsies were obtained from 37 different sites within the tumors in 12 patients. Age, sex, Karnofsky Performance Scale status, extent of removal, chemotherapeutic methods, and MGMT promoter methylation and protein expression were analyzed as prognostic factors.


RESULTS
The total median survival was 15.8 months (range, 12.6-19.1 months). The results of MSP were the same at various sites in 12 patients. A correlation between MSP and immunohistochemical staining was observed in 50% of the patients. In 73 patients, negative MGMT expression was detected in 70.5% of 44 patients with MGMT promoter methylation, and positive expression was observed in 55.2% of the 29 patients with unmethylated promoters. Multivariate analysis revealed that the extent of removal (P = 0.001) and the combination of MGMT promoter methylation and negative MGMT expression (median survival, 20.06 months; P = 0.006) were significantly associated with longer survival.


CONCLUSIONS
We report the feasibility of using MSP combined with immunohistochemical staining as a prognostic factor. The results of the present study suggest that MGMT promoter methylation in combination with negative MGMT expression might be a good prognostic factor in patients with glioblastoma.
Cao
Van Thang
VT
Brain Tumor Research Laboratory and Research Institute of Medical Sciences, Chonnam National University, Hwasun Hospital and Medical School, Gwangju, Republic of Korea.
Jung
Tae-Young
TY
Jung
Shin
S
Jin
Shu-Guang
SG
Moon
Kyung-Sub
KS
Kim
In-Young
IY
Kang
Sam-Suk
SS
Park
Chang-Soo
CS
Lee
Kyung-Hwa
KH
Chae
Hong-Jae
HJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D003131:Combined Modality Therapy; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011878:Radiotherapy; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide