Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas

Nishikawa, Tadahiro; Watanabe, Reiko; Kitano, Yasushi; Yamamichi, Akane; Motomura, Kazuya; Ohka, Fumiharu; Hashimoto, Masaki; Kato, Akira; Yamaguchi, Junya; Maeda, Sachi; Kibe, Yuji; Saito, Ryuta; Wakabayashi, Toshihiko; Kato, Yoshinori; Sato, S.; Ogino, Tomoyoshi; Natsume, Atsushi; Ito, Ichiro

doi:10.1007/s10014-021-00418-x

Cited by 8 publications

(10 citation statements)

References 30 publications

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“…15,[30][31][32] Because we did not sequence all cases, we are not able to talk about probable false positive IHC reactions such as those reported by Nishikawa. 14 In a series evaluated by Ebrahimi et al, 24 among 345 IDH mutant tumors, IDH1 P. R132 H was detected in 88% (305/345). Less common forms were as follow: IDH1 P. R132 C:3.3%; IDH1 P. R132 G:0.3%; IDH1 P. R132 S: 0.1%; and IDH2: 0.43%.…”

Section: Discussionmentioning

confidence: 96%

“…In this study, the interpretation of IHC markers was done as follows: 14 IDH1: positive reaction was defined as both nuclear and cytoplasmic reaction.…”

Section: Methodsmentioning

confidence: 99%

“…Also, CDKN2A/B homozygous deletion, EGFR amplification, and TERT promoter mutation should be considered for the diagnosis of high-grade glioma along with mitosis, necrosis, and microvascular proliferation. 8,11,13,14 Following recent changes, molecular parameters including ATRX, P53, and IDH mutation status, absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma. 4,15 However, comprehensive molecular testing in centers with limited resources is a great challenge.…”

mentioning

confidence: 99%

“…IDH mutation plays a crucial role in glioma classification, 12 and in association with 1p/19q co-deletion, has captured biological characteristics superior and more reliable than histology in adult diffuse glioma classification. Also, CDKN2A/B homozygous deletion, EGFR amplification, and TERT promoter mutation should be considered for the diagnosis of high-grade glioma along with mitosis, necrosis, and microvascular proliferation 8,11,13,14 …”

mentioning

confidence: 99%

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Practice of IDH1, ATRX, and P53 Immunohistochemistry in Integrated Diagnosis of Adult Diffuse Gliomas: Single Center Study

Shabanzadeh nejabad,

Mabroukzadeh kavari,

Saffar

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Diffuse gliomas exhibit different molecular and genetic profiles with a wide range of heterogeneity and prognosis. Recently, molecular parameters including ATRX, P53, and IDH mutation status or absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma. In the present study, we tried to analyze the routine practice of the above-mentioned molecular markers focusing on the IHC method in cases of adult diffuse gliomas to evaluate their utility in the integrated diagnosis of adult diffuse gliomas. In total, 134 cases of adult diffuse glioma were evaluated. Using the IHC method, 33,12, and 12 cases of IDH mutant Astrocytoma grade 2, 3, 4, and 45 cases of gliobalstoma, IDH wild type, were molecularly diagnosed. By adding the FISH study for 1p/19q co-deletion, 9 and 8 cases of oligodendroglioma grade 2 and 3 also were included. Two IDH mutant cases were negative for IDH1 in IHC but revealed a positive mutation in further molecular testing. Finally, we were not able to incorporate a complete integrated diagnosis in 16/134(11.94%) of cases. The main molecularly unclassified group was histologically high-grade diffuse glial tumors in patients less than 55 years old and negative IDH1 immunostaining. P53 was positive in 23/33 grade 2, 4/12 grade 3, and 7/12 grade 4 astrocytomas, respectively. Four out of 45 glioblastomas showed positive immunostain, and all oligodendrogliomas were negative. In conclusion, a panel of IHC markers for IDH1 R132H, P53, and ATRX significantly improves the molecular classification of adult diffuse gliomas in daily practice and can be used as a tool to select limited cases for co-deletion testing in the low resources area.

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Section: Discussionmentioning

confidence: 96%

“…In this study, the interpretation of IHC markers was done as follows: 14 IDH1: positive reaction was defined as both nuclear and cytoplasmic reaction.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Practice of IDH1, ATRX, and P53 Immunohistochemistry in Integrated Diagnosis of Adult Diffuse Gliomas: Single Center Study

Shabanzadeh nejabad,

Mabroukzadeh kavari,

Saffar

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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show abstract

“…Of them, the clone H09 showed better performance and was used most frequently as a commercialized antibody. While a promising sensitivity was obtained by the test on routine formalin-fixed, paraffin-embedded (FFPE) tissue sections [ 17 , 18 , 22 , 23 , 24 ], some limitations of H09 have been described during its applications, including its cross-reactivity with other IDH1/2 mutants [ 16 , 20 , 25 , 26 , 27 ], background stain [ 25 , 28 , 29 , 30 ], and frequent false negativity in FFPE frozen samples following freezing and thawing procedures [ 15 , 31 ]. Evidently, further studies are needed into IHC applications of this antibody in terms of specificity and limitations.…”

Section: Introductionmentioning

confidence: 99%

Characterization of an IDH1 R132H Rabbit Monoclonal Antibody, MRQ-67, and Its Applications in the Identification of Diffuse Gliomas

et al. 2023

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The current diagnosis of diffuse glioma involves isocitrate dehydrogenase (IDH) mutation testing. Most IDH mutant gliomas carry a G-to-A mutation at IDH1 position 395, resulting in the R132H mutant. R132H immunohistochemistry (IHC), therefore, is used to screen for the IDH1 mutation. In this study, the performance of MRQ-67, a recently generated IDH1 R132H antibody, was characterized in comparison with H09, a frequently used clone. Selective binding was demonstrated by an enzyme-linked immunosorbent assay for MRQ-67 to the R132H mutant, with an affinity higher than that for H09. By Western and dot immunoassays, MRQ-67 was found to bind specifically to the IDH1 R1322H, with a higher capacity than H09. IHC testing with MRQ-67 demonstrated a positive signal in most diffuse astrocytomas (16/22), oligodendrogliomas (9/15), and secondary glioblastomas tested (3/3), but not in primary glioblastomas (0/24). While both clones demonstrated a positive signal with similar patterns and equivalent intensities, H09 exhibited a background stain more frequently. DNA sequencing on 18 samples showed the R132H mutation in all IHC positive cases (5/5), but not in negative cases (0/13). These results demonstrate that MRQ-67 is a high-affinity antibody suitable for specific detection of the IDH1 R132H mutant by IHC and with less background as compared with H09.

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Clinical and imaging characteristics of supratentorial glioma with IDH2 mutation

Ikeda,

Sakata,

Arakawa

et al. 2024

Neuroradiology

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Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas

Cited by 8 publications

References 30 publications

Practice of IDH1, ATRX, and P53 Immunohistochemistry in Integrated Diagnosis of Adult Diffuse Gliomas: Single Center Study

Practice of IDH1, ATRX, and P53 Immunohistochemistry in Integrated Diagnosis of Adult Diffuse Gliomas: Single Center Study

Characterization of an IDH1 R132H Rabbit Monoclonal Antibody, MRQ-67, and Its Applications in the Identification of Diffuse Gliomas

Clinical and imaging characteristics of supratentorial glioma with IDH2 mutation

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