H3K27me3 immunostaining is diagnostic and prognostic in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology.

Oligodendroglioma is defined by IDH mutation and 1p/19q codeletion. The latter is mutually exclusive to ATRX immunohistochemical loss and has been recently associated with the loss of H3K27me3 immunostaining. We aimed to assess the diagnostic and prognostic value of H3K27me3 immuno-expression in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology. H3K27me3 immunostaining was performed in 69 diffuse gliomas with oligodendroglial (n = 62) or oligoastrocytic (n = 7) morphology. The integration with routinely assessed IDH mutations, ATRX immunostaining, and 1p/19q codeletion classified these cases as 60 oligodendroglial and 9 astrocytic. H3K27me3 was lost in 58/60 oligodendrogliomas with retained (n = 47) or non-conclusive (n = 11) ATRX staining, 3/6 IDH-mutant astrocytomas with ATRX loss, and 3/3 IDH-wt astrocytomas. H3K27me3 was retained in 2/60 oligodendrogliomas with retained ATRX, and in 3/6 IDH-mutant astrocytomas, two of which had lost and one retained ATRX. The combination of H3K27me3 and ATRX immunostainings with IDH mutational status correctly classified 55/69 (80%) cases. In IDH-mutant gliomas, ATRX loss indicates astrocytic phenotype, while ATRX retention and H3K27me3 loss identify oligodendroglial phenotype. Only 14 (20%) IDH-mutant cases with retained ATRX and H3K27me3 or inconclusive ATRX immunostaining would have requested 1p/19q codeletion testing to be classified. Furthermore, H3K27me3 retention was associated with significantly shorter relapse-free survival (P < 0.0001), independently from IDH mutation or 1p/19q codeletion (P < 0.005). Our data suggest that adding H3K27me3 immunostaining to the diagnostic workflow of diffuse gliomas with oligodendroglial or mixed morphology is useful for drastically reducing the number of cases requiring 1p/19q codeletion testing and providing relevant prognostic information.

Ammendola S ，Caldonazzi N ，Simbolo M ，Piredda ML ，Brunelli M ，Poliani PL ，Pinna G ，Sala F ，Ghimenton C ，Scarpa A ，Barresi V ... -  《-》

Loss of H3K27 trimethylation is frequent in IDH1-R132H but not in non-canonical IDH1/2 mutated and 1p/19q codeleted oligodendroglioma: a Japanese cohort study.

Habiba U ，Sugino H ，Yordanova R ，Ise K ，Tanei ZI ，Ishida Y ，Tanikawa S ，Terasaka S ，Sato KI ，Kamoshima Y ，Katoh M ，Nagane M ，Shibahara J ，Tsuda M ，Tanaka S ... -  《Acta Neuropathologica Communications》

ATRX immunohistochemistry can help refine 'not elsewhere classified' categorisation for grade II/III gliomas.

Burford C ，Laxton R ，Sidhu Z ，Aizpurua M ，King A ，Bodi I ，Ashkan K ，Al-Sarraj S ... -  《-》

HIP1R and vimentin immunohistochemistry predict 1p/19q status in IDH-mutant glioma.

IDH-mutant gliomas are separate based on the codeletion of the chromosomal arms 1p and 19q into oligodendrogliomas IDH-mutant 1p/19q-codeleted and astrocytomas IDH-mutant. While nuclear loss of ATRX expression excludes 1p/19q codeletion, its limited sensitivity prohibits to conclude on 1p/19q status in tumors with retained nuclear ATRX expression. Employing mass spectrometry based proteomic analysis in a discovery series containing 35 fresh frozen and 72 formalin fixed and paraffin embedded tumors with established IDH and 1p/19q status, potential biomarkers were discovered. Subsequent validation immunohistochemistry was conducted on two independent series (together 77 oligodendrogliomas IDH-mutant 1p/19q-codeleted and 92 astrocytomas IDH-mutant). We detected highly specific protein patterns distinguishing oligodendroglioma and astrocytoma. In these patterns, high HIP1R and low vimentin levels were observed in oligodendroglioma while low HIP1R and high vimentin levels occurred in astrocytoma. Immunohistochemistry for HIP1R and vimentin expression in 35 cases from the FFPE discovery series confirmed these findings. Blinded evaluation of the validation cohorts predicted the 1p/19q status with a positive and negative predictive value as well as an accuracy of 100% in the first cohort and with a positive predictive value of 83%; negative predictive value of 100% and an accuracy of 92% in the second cohort. Nuclear ATRX loss as marker for astrocytoma increased the sensitivity to 96% and the specificity to 100%. We demonstrate that immunohistochemistry for HIP1R, vimentin, and ATRX predict 1p/19q status with 100% specificity and 95% sensitivity and therefore, constitutes a simple and inexpensive approach to the classification of IDH-mutant glioma.

Felix M ，Friedel D ，Jayavelu AK ，Filipski K ，Reinhardt A ，Warnken U ，Stichel D ，Schrimpf D ，Korshunov A ，Wang Y ，Kessler T ，Etminan N ，Unterberg A ，Herold-Mende C ，Heikaus L ，Sahm F ，Wick W ，Harter PN ，von Deimling A ，Reuss DE ... -  《-》

TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations.

Arita H ，Matsushita Y ，Machida R ，Yamasaki K ，Hata N ，Ohno M ，Yamaguchi S ，Sasayama T ，Tanaka S ，Higuchi F ，Iuchi T ，Saito K ，Kanamori M ，Matsuda KI ，Miyake Y ，Tamura K ，Tamai S ，Nakamura T ，Uda T ，Okita Y ，Fukai J ，Sakamoto D ，Hattori Y ，Pareira ES ，Hatae R ，Ishi Y ，Miyakita Y ，Tanaka K ，Takayanagi S ，Otani R ，Sakaida T ，Kobayashi K ，Saito R ，Kurozumi K ，Shofuda T ，Nonaka M ，Suzuki H ，Shibuya M ，Komori T ，Sasaki H ，Mizoguchi M ，Kishima H ，Nakada M ，Sonoda Y ，Tominaga T ，Nagane M ，Nishikawa R ，Kanemura Y ，Kuchiba A ，Narita Y ，Ichimura K ... -  《Acta Neuropathologica Communications》