IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors
A total of 343 brain tumors were studied for IDH1 and IDH2 mutations by direct sequencing and for protein expression by immunohistochemistry with mIDH1 R132H antibody. Of these, 287 were gliomas (17 pilocytic astrocytomas, 13 grade II and 5 grade III astrocytomas, 167 primary (pGBMs) and 19 secondar...
Saved in:
Published in | Journal of neuro-oncology Vol. 105; no. 2; pp. 345 - 357 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.11.2011
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | A total of 343 brain tumors were studied for
IDH1
and
IDH2
mutations by direct sequencing and for protein expression by immunohistochemistry with mIDH1
R132H
antibody. Of these, 287 were gliomas (17 pilocytic astrocytomas, 13 grade II and 5 grade III astrocytomas, 167 primary (pGBMs) and 19 secondary (sGBMs) glioblastomas, 36 grade II and 26 grade III oligodendrogliomas and 4 grade II–III oligoastrocytomas). In gliomas,
IDH1
mutations at codon R132 were identified in 22.3%, of which 93.7% were c.395G>A (p.R132H). Mutations were more frequent in oligodendrogliomas (53.2%) than in astrocytic tumors (22.8%) and in sGBMs (84.2%) upon pGBMs (1.8%). There was a statistically significant correlation between mIDH1
R132H
antibody immunostaining and the relevant mutation c.395G>A (p.R132H) (
P
= 0.0001). No mutations were identified in non-glial tumors which were also negative to immunohistochemistry, with the exception of one PNET. A c.515G>T (p.R172M) mutation of the
IDH2
gene was only identified in a grade II oligodendroglioma patient which was wild-type for
IDH1
. A direct correlation with
MGMT
promoter hypermethylation status and an inverse correlation with
EGFR
amplification was found, whereas the relationships with 1p/19q co-deletion and
TP53
mutations only showed a trend toward correlation. In all gliomas, a positive correlation was found between
IDH1
mutations and a young age (
P
= 0.0001). In contrast, a correlation with overall survival could only be obtained in low-grade gliomas. Immunohistochemistry appeared to be useful in differential diagnoses, especially toward non-tumor pathologic nervous tissue, and in recognizing infiltrating glioma cells. The mIDH1
R132H
antibody positivity was complementary with Cyclin D1 expression. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0167-594X 1573-7373 |
DOI: | 10.1007/s11060-011-0596-3 |