BIOM-11. PROGNOSTIC VALUE OF H3K27ME3 AND EZH2 IN ASTROCYTOMA, IDH-MUTANT

Abstract BACKGROUND H3K27 trimethylation (H3K27me3), catalyzed by EZH2, regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a surrogate marker in pathology for diffuse midline glioma, ependymoma. However, the clinical value of H3K27me3 and EZH2 in astrocytoma, IDH-mutant has...

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Veröffentlicht in:Neuro-oncology (Charlottesville, Va.) Va.), 2024-11, Vol.26 (Supplement_8), p.viii21-viii21
Hauptverfasser: Onishi, Shumpei, Yamasaki, Fumiyuki, Amatya, Vishwa Jeet, Yonezawa, Ushio, Taguchi, Akira, Ozono, Iori, Khairunnisa, Novita Ikbar, Go, Yukari, Takeshima, Yukio, Horie, Nobutaka
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container_end_page viii21
container_issue Supplement_8
container_start_page viii21
container_title Neuro-oncology (Charlottesville, Va.)
container_volume 26
creator Onishi, Shumpei
Yamasaki, Fumiyuki
Amatya, Vishwa Jeet
Yonezawa, Ushio
Taguchi, Akira
Ozono, Iori
Khairunnisa, Novita Ikbar
Go, Yukari
Takeshima, Yukio
Horie, Nobutaka
description Abstract BACKGROUND H3K27 trimethylation (H3K27me3), catalyzed by EZH2, regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a surrogate marker in pathology for diffuse midline glioma, ependymoma. However, the clinical value of H3K27me3 and EZH2 in astrocytoma, IDH-mutant has not been reported. The aim of this study was to evaluate the clinical significance of H3K27me3 and EZH2 in astrocytoma, IDH-mutant. METHODS A total of 30 patients with astrocytoma, IDH-mutant treated at our institute were included. The patients were divided into 2 groups according to the expression of immunohistochemistry (IHC) for H3K27me3. The following factors were analyzed; age, WHO grade, IHC for EZH2, CDKN2A status, ki67-index and extent of resection. The CDKN2A status was diagnosed by IHC for MTAP and was confirmed by NGS-based CGP test in some cases. Kaplan–Meier analysis and Cox regression analysis were performed to analyze overall survival (OS) and progression-free survival (PFS). RESULTS According to WHO classification 2021, astrocytomas were classified as follows: WHO grade2: 20 cases, grade 3: 2 cases, grade 4: 8 cases. Seventeen patients were identified as H3K27me3 positive, while fourteen patients were classified as H3K27me3 negative. The proportion of WHO grade 3 or 4 and ki-67 index were significantly higher in the H3K27me3 positive group (p=0.0011, 0.0036, respectively). OS and PFS were significantly longer in H3K27me3 positive group (p=0.0379, 0.0025). Furthermore, in the analysis of WHO grade 2/3, double-positive expression of H3K27me3 and EZH2 showed significantly shorter PFS and OS than the other group (p=0.0114 and 0.0068, respectively). In Cox regression analysis, H3K27me3 showed the highest likelihood ratio for OS (p=0.01061). CONCLUSIONS In Astrocytoma, IDH-mutant, the H3K27me3 positive group showed poor prognosis than H3K27me3 negative group. In addition, patients with double-positive expression of H3K27me3 and EZH2 demonstrated more unfavorable prognosis. H3K27me3 and EZH2 could be prognostic markers for astrocytoma, IDH-mutant.
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PROGNOSTIC VALUE OF H3K27ME3 AND EZH2 IN ASTROCYTOMA, IDH-MUTANT</title><source>Oxford Journals【Remote access available】</source><creator>Onishi, Shumpei ; Yamasaki, Fumiyuki ; Amatya, Vishwa Jeet ; Yonezawa, Ushio ; Taguchi, Akira ; Ozono, Iori ; Khairunnisa, Novita Ikbar ; Go, Yukari ; Takeshima, Yukio ; Horie, Nobutaka</creator><creatorcontrib>Onishi, Shumpei ; Yamasaki, Fumiyuki ; Amatya, Vishwa Jeet ; Yonezawa, Ushio ; Taguchi, Akira ; Ozono, Iori ; Khairunnisa, Novita Ikbar ; Go, Yukari ; Takeshima, Yukio ; Horie, Nobutaka</creatorcontrib><description>Abstract BACKGROUND H3K27 trimethylation (H3K27me3), catalyzed by EZH2, regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a surrogate marker in pathology for diffuse midline glioma, ependymoma. However, the clinical value of H3K27me3 and EZH2 in astrocytoma, IDH-mutant has not been reported. The aim of this study was to evaluate the clinical significance of H3K27me3 and EZH2 in astrocytoma, IDH-mutant. METHODS A total of 30 patients with astrocytoma, IDH-mutant treated at our institute were included. The patients were divided into 2 groups according to the expression of immunohistochemistry (IHC) for H3K27me3. The following factors were analyzed; age, WHO grade, IHC for EZH2, CDKN2A status, ki67-index and extent of resection. The CDKN2A status was diagnosed by IHC for MTAP and was confirmed by NGS-based CGP test in some cases. Kaplan–Meier analysis and Cox regression analysis were performed to analyze overall survival (OS) and progression-free survival (PFS). RESULTS According to WHO classification 2021, astrocytomas were classified as follows: WHO grade2: 20 cases, grade 3: 2 cases, grade 4: 8 cases. Seventeen patients were identified as H3K27me3 positive, while fourteen patients were classified as H3K27me3 negative. The proportion of WHO grade 3 or 4 and ki-67 index were significantly higher in the H3K27me3 positive group (p=0.0011, 0.0036, respectively). OS and PFS were significantly longer in H3K27me3 positive group (p=0.0379, 0.0025). Furthermore, in the analysis of WHO grade 2/3, double-positive expression of H3K27me3 and EZH2 showed significantly shorter PFS and OS than the other group (p=0.0114 and 0.0068, respectively). In Cox regression analysis, H3K27me3 showed the highest likelihood ratio for OS (p=0.01061). CONCLUSIONS In Astrocytoma, IDH-mutant, the H3K27me3 positive group showed poor prognosis than H3K27me3 negative group. In addition, patients with double-positive expression of H3K27me3 and EZH2 demonstrated more unfavorable prognosis. H3K27me3 and EZH2 could be prognostic markers for astrocytoma, IDH-mutant.</description><identifier>ISSN: 1522-8517</identifier><identifier>EISSN: 1523-5866</identifier><identifier>DOI: 10.1093/neuonc/noae165.0084</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><ispartof>Neuro-oncology (Charlottesville, Va.), 2024-11, Vol.26 (Supplement_8), p.viii21-viii21</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Onishi, Shumpei</creatorcontrib><creatorcontrib>Yamasaki, Fumiyuki</creatorcontrib><creatorcontrib>Amatya, Vishwa Jeet</creatorcontrib><creatorcontrib>Yonezawa, Ushio</creatorcontrib><creatorcontrib>Taguchi, Akira</creatorcontrib><creatorcontrib>Ozono, Iori</creatorcontrib><creatorcontrib>Khairunnisa, Novita Ikbar</creatorcontrib><creatorcontrib>Go, Yukari</creatorcontrib><creatorcontrib>Takeshima, Yukio</creatorcontrib><creatorcontrib>Horie, Nobutaka</creatorcontrib><title>BIOM-11. PROGNOSTIC VALUE OF H3K27ME3 AND EZH2 IN ASTROCYTOMA, IDH-MUTANT</title><title>Neuro-oncology (Charlottesville, Va.)</title><description>Abstract BACKGROUND H3K27 trimethylation (H3K27me3), catalyzed by EZH2, regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a surrogate marker in pathology for diffuse midline glioma, ependymoma. However, the clinical value of H3K27me3 and EZH2 in astrocytoma, IDH-mutant has not been reported. The aim of this study was to evaluate the clinical significance of H3K27me3 and EZH2 in astrocytoma, IDH-mutant. METHODS A total of 30 patients with astrocytoma, IDH-mutant treated at our institute were included. The patients were divided into 2 groups according to the expression of immunohistochemistry (IHC) for H3K27me3. The following factors were analyzed; age, WHO grade, IHC for EZH2, CDKN2A status, ki67-index and extent of resection. The CDKN2A status was diagnosed by IHC for MTAP and was confirmed by NGS-based CGP test in some cases. Kaplan–Meier analysis and Cox regression analysis were performed to analyze overall survival (OS) and progression-free survival (PFS). RESULTS According to WHO classification 2021, astrocytomas were classified as follows: WHO grade2: 20 cases, grade 3: 2 cases, grade 4: 8 cases. Seventeen patients were identified as H3K27me3 positive, while fourteen patients were classified as H3K27me3 negative. The proportion of WHO grade 3 or 4 and ki-67 index were significantly higher in the H3K27me3 positive group (p=0.0011, 0.0036, respectively). OS and PFS were significantly longer in H3K27me3 positive group (p=0.0379, 0.0025). Furthermore, in the analysis of WHO grade 2/3, double-positive expression of H3K27me3 and EZH2 showed significantly shorter PFS and OS than the other group (p=0.0114 and 0.0068, respectively). In Cox regression analysis, H3K27me3 showed the highest likelihood ratio for OS (p=0.01061). CONCLUSIONS In Astrocytoma, IDH-mutant, the H3K27me3 positive group showed poor prognosis than H3K27me3 negative group. In addition, patients with double-positive expression of H3K27me3 and EZH2 demonstrated more unfavorable prognosis. H3K27me3 and EZH2 could be prognostic markers for astrocytoma, IDH-mutant.</description><issn>1522-8517</issn><issn>1523-5866</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqN0E1OwzAQhmELgUQpnICND4BTjx3_ZBnStIloYtS6SLCJ0jiWQNBUibrg9lDSA7Ca2bzf4kHoHmgANOKzfXvs9s1s39UtSBFQqsMLNAHBOBFaysu_nxEtQF2jm2H4oJSBkDBB-WNuCgIQ4Oe1WZZmY_MEv8SrbYrNAmf8iaki5Tgu5zh9yxjOSxxv7Nokr9YU8QPO5xkptjYu7S268vXn0N6d7xTZRWqTjKzMMk_iFWk0D4lrJVUOwlDpyHPHd0qCdLoRNXc1bXeKqpDXaudDBtqLSEaOO-qVklIr5h2fIj7ONn03DH3rq0P__lX33xXQ6oRRjRjVGaM6YfxWwVh1x8O_gh-se10Q</recordid><startdate>20241111</startdate><enddate>20241111</enddate><creator>Onishi, Shumpei</creator><creator>Yamasaki, Fumiyuki</creator><creator>Amatya, Vishwa Jeet</creator><creator>Yonezawa, Ushio</creator><creator>Taguchi, Akira</creator><creator>Ozono, Iori</creator><creator>Khairunnisa, Novita Ikbar</creator><creator>Go, Yukari</creator><creator>Takeshima, Yukio</creator><creator>Horie, Nobutaka</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20241111</creationdate><title>BIOM-11. PROGNOSTIC VALUE OF H3K27ME3 AND EZH2 IN ASTROCYTOMA, IDH-MUTANT</title><author>Onishi, Shumpei ; Yamasaki, Fumiyuki ; Amatya, Vishwa Jeet ; Yonezawa, Ushio ; Taguchi, Akira ; Ozono, Iori ; Khairunnisa, Novita Ikbar ; Go, Yukari ; Takeshima, Yukio ; Horie, Nobutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c834-de607d144789f3d3b7616d8c5a3da0eb70743a7bf4218f5969d3d0f7766872fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Onishi, Shumpei</creatorcontrib><creatorcontrib>Yamasaki, Fumiyuki</creatorcontrib><creatorcontrib>Amatya, Vishwa Jeet</creatorcontrib><creatorcontrib>Yonezawa, Ushio</creatorcontrib><creatorcontrib>Taguchi, Akira</creatorcontrib><creatorcontrib>Ozono, Iori</creatorcontrib><creatorcontrib>Khairunnisa, Novita Ikbar</creatorcontrib><creatorcontrib>Go, Yukari</creatorcontrib><creatorcontrib>Takeshima, Yukio</creatorcontrib><creatorcontrib>Horie, Nobutaka</creatorcontrib><collection>CrossRef</collection><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Onishi, Shumpei</au><au>Yamasaki, Fumiyuki</au><au>Amatya, Vishwa Jeet</au><au>Yonezawa, Ushio</au><au>Taguchi, Akira</au><au>Ozono, Iori</au><au>Khairunnisa, Novita Ikbar</au><au>Go, Yukari</au><au>Takeshima, Yukio</au><au>Horie, Nobutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BIOM-11. PROGNOSTIC VALUE OF H3K27ME3 AND EZH2 IN ASTROCYTOMA, IDH-MUTANT</atitle><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle><date>2024-11-11</date><risdate>2024</risdate><volume>26</volume><issue>Supplement_8</issue><spage>viii21</spage><epage>viii21</epage><pages>viii21-viii21</pages><issn>1522-8517</issn><eissn>1523-5866</eissn><abstract>Abstract BACKGROUND H3K27 trimethylation (H3K27me3), catalyzed by EZH2, regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a surrogate marker in pathology for diffuse midline glioma, ependymoma. However, the clinical value of H3K27me3 and EZH2 in astrocytoma, IDH-mutant has not been reported. The aim of this study was to evaluate the clinical significance of H3K27me3 and EZH2 in astrocytoma, IDH-mutant. METHODS A total of 30 patients with astrocytoma, IDH-mutant treated at our institute were included. The patients were divided into 2 groups according to the expression of immunohistochemistry (IHC) for H3K27me3. The following factors were analyzed; age, WHO grade, IHC for EZH2, CDKN2A status, ki67-index and extent of resection. The CDKN2A status was diagnosed by IHC for MTAP and was confirmed by NGS-based CGP test in some cases. Kaplan–Meier analysis and Cox regression analysis were performed to analyze overall survival (OS) and progression-free survival (PFS). RESULTS According to WHO classification 2021, astrocytomas were classified as follows: WHO grade2: 20 cases, grade 3: 2 cases, grade 4: 8 cases. Seventeen patients were identified as H3K27me3 positive, while fourteen patients were classified as H3K27me3 negative. The proportion of WHO grade 3 or 4 and ki-67 index were significantly higher in the H3K27me3 positive group (p=0.0011, 0.0036, respectively). OS and PFS were significantly longer in H3K27me3 positive group (p=0.0379, 0.0025). Furthermore, in the analysis of WHO grade 2/3, double-positive expression of H3K27me3 and EZH2 showed significantly shorter PFS and OS than the other group (p=0.0114 and 0.0068, respectively). In Cox regression analysis, H3K27me3 showed the highest likelihood ratio for OS (p=0.01061). CONCLUSIONS In Astrocytoma, IDH-mutant, the H3K27me3 positive group showed poor prognosis than H3K27me3 negative group. In addition, patients with double-positive expression of H3K27me3 and EZH2 demonstrated more unfavorable prognosis. H3K27me3 and EZH2 could be prognostic markers for astrocytoma, IDH-mutant.</abstract><cop>US</cop><pub>Oxford University Press</pub><doi>10.1093/neuonc/noae165.0084</doi></addata></record>
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