Confounding factors in diagnostics of MGMT promoter methylation status in glioblastomas in stereotactic biopsies.
BACKGROUND
In nonresectable glioblastoma (GBM), stereotactic biopsies are performed to retrieve tissue for diagnostic purposes. The analysis of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation adds prognostic and predictive information.


OBJECTIVE
The aim of the study was to detect confounding factors that limit the number of conclusive MGMT promoter methylation results.


METHODS
We analyzed 71 consecutive GBM patients undergoing stereotactic biopsy on whom MGMT analysis was performed by methylation-specific polymerase chain reaction. Specimens were correlated to imaging by coregistration and prospective documentation of biopsy localization. Our findings were validated in an additional 62 GBM stereotactic biopsies.


RESULTS
Our results demonstrate that the best MGMT promoter methylation results were obtained from samples (n = 71) taken in a tangential manner from tumor areas showing contrast enhancement in magnetic resonance imaging. In the additional validation series of 62 stereotactically biopsied GBM, we were able to increase the rate of conclusive MGMT promoter methylation results from 76.1 to 85.48% by strictly planning the route of biopsy in a tangential manner if possible.


CONCLUSIONS
These results underline that within the contrast-enhanced tumor part, choosing the trajectory in a tangential manner increases the diagnostic yield for conclusive MGMT promoter methylation analyses in stereotactic biopsies as a basis for patient stratification and individualized therapy.
Department of Neurosurgery, Goethe University Frankfurt, Frankfurt/Main, Germany.
Lutz M
LM
Weise
Patrick N
PN
Harter
Sebastian
S
Eibach
Anne K
AK
Braczynski
Maika
M
Dunst
Johannes
J
Rieger
Oliver
O
Bähr
Elke
E
Hattingen
Joachim P
JP
Steinbach
Karl H
KH
Plate
Volker
V
Seifert
Michel
M
Mittelbronn
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011446:Prospective Studies; D012042:Registries; D012189:Retrospective Studies; D013238:Stereotaxic Techniques / Q000592:standards; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes