Interlaboratory comparison of IDH mutation detection.
Isocitrate dehydrogenase (IDH) mutational testing is becoming increasingly important. For this, robust and reliable assays are needed. We tested the variation of results between six laboratories of testing for IDH mutations. Each laboratory received five unstained slides from 31 formalin-fixed paraffin-embedded (FFPE) glioma samples, and followed its own standard IDH diagnostic routine. All laboratories used immunohistochemistry (IHC) with an antibody against the most frequent IDH1 mutation (R132H) as a first step. Three laboratories then sequenced only IHC negative cases while the others sequenced all cases. Based on the overall analysis, 13 samples from 11 tumors had an R132H mutation and one tumor showed an R132G mutation. Results of IHC for IDH1 R132H mutations in all six laboratories were completely in agreement, and identified all R132H mutations. Upon sequencing the results of two laboratories deviated from those of the others. After a review of the entire diagnostic process, on repeat (blinded) testing one laboratory was completely in agreement with the overall result. A change in technique did only partially improve the results in the other laboratory. IHC for the IDH1 R132H mutation is very reliable and consistent across laboratories. IDH sequencing procedures yielded inconsistent results in 2 out of 6 laboratories. Quality assurance is pivotal before IDH testing is made part of clinical management of patients.
Department of Neurology/Neuro-Oncology, Erasmus MC - Cancer Institute, Groene Hilledijk 301, 3075EA, Rotterdam, the Netherlands. m.vandenbent@erasmusmc.nl
Martin J
MJ
van den Bent
C
C
Hartmann
Matthias
M
Preusser
Thomas
T
Ströbel
Hendrikus J
HJ
Dubbink
Johan M
JM
Kros
Andreas
A
von Deimling
Blandine
B
Boisselier
Marc
M
Sanson
Kevin C
KC
Halling
Kristin L
KL
Diefes
Kenneth
K
Aldape
Caterina
C
Giannini
D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D007753:Laboratories / Q000592:standards*; D009154:Mutation / Q000235:genetics*; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human