title: Usefulness of MS-MLPA for detection of MGMT promoter methylation in the evaluation of pseudoprogression in glioblastoma patients.
abstract: Pseudoprogression is a major diagnostic dilemma in current treatment protocols for malignant gliomas that involve concurrent chemoradiotherapy. We hypothesized that methylation-specific multiplex ligation probe amplification (MS-MLPA), an assay that permits semiquantitative evaluation of promoter methylation, may be used to diagnose pseudoprogression based on the quantification of the methylation status of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter. We examined the methylation ratio of the MGMT promoter with MS-MLPA in 48 samples from glioblastoma patients. The results were compared with those from methylation-specific polymerase chain reaction (MSP), and protein levels were confirmed by immunohistochemical staining. We then evaluated the correlation between those molecular signatures and clinical outcomes. With regard to radiological progression after chemoradiotherapy, the diagnostic accuracy of the MS-MLPA method was 80% (using a cut-off value of 0.2). These results are better than those obtained with MSP (diagnostic accuracy of 68%). Combining the MS-MLPA and MSP methods resulted in a diagnostic accuracy of 93% for the identification of pseudoprogression among patients to whom these results were coherent. These results demonstrate that MS-MLPA is a useful method to predict radiological progression vs pseudoprogression in glioblastoma patients and that the interpretation of these results in combination with MSP results will provide good practical guidelines for clinical decision making in glioblastoma treatment.
authors.affiliation: Department of Neurosurgery, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea. nsckpark@paran.com
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.forename: JinWook
authors.initials: J
authors.lastname: Kim
authors.forename: Su Youn
authors.initials: SY
authors.lastname: Yim
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Lee
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Han
authors.forename: Chae-Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Dong Gyu
authors.initials: DG
authors.lastname: Kim
authors.forename: Hee-Won
authors.initials: HW
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D019175:DNA Methylation; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D015336:Molecular Probe Techniques; D021141:Nucleic Acid Amplification Techniques / Q000706:statistics & numerical data*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide