Reliability assessment of methylthioadenosine phosphorylase immunohistochemistry as a surrogate biomarker for CDKN2A homozygous deletion in adult-type IDH-mutant diffuse gliomas

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2023-12-19 DOI:10.1093/jnen/nlad109
Fatma Gundogdu, Berrin Babaoglu, Figen Soylemezoglu
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Abstract

According to the 2021 World Health Organization classification of brain tumors, astrocytomas containing a CDKN2A/B homozygous deletion (HD) are designated as grade 4 even when no microvascular proliferation and/or necrosis is present. In this study, we aimed to investigate the relationship between CDKN2A HD and loss of methylthioadenosine phosphorylase (MTAP) expression in adult-type IDH-mutant gliomas and to assess the sensitivity and specificity of MTAP immunohistochemistry (IHC) along with interobserver agreement as a surrogate biomarker for CDKN2A HD. Eighty-eight astrocytomas and 71 oligodendrogliomas cases that were diagnosed between 2014 and 2021 at Hacettepe University were selected and tissue microarrays were conducted to perform CDKN2A fluorescence in situ hybridization and MTAP IHC. Twenty-five (15.7%) cases harbored CDKN2A HD. MTAP loss was detected in 28 (15.7%) cases by the first observer and 27 (17%) cases by the second observer. The sensitivity and specificity of MTAP were calculated as 88% and 95.52%-96.27% for 2 observers. A very good/perfect agreement was noted between the observers (Cohen kappa coefficient = 0.938). Intratumoral heterogeneity was observed in 4 cases. MTAP IHC was found to be a reliable surrogate biomarker as a possible alternative to CDKN2A HD identification with a high sensitivity and specificity along with high interobserver agreement.
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将甲硫腺苷磷酸化酶免疫组化作为成人型 IDH 突变弥漫性胶质瘤 CDKN2A 同源缺失的替代生物标记物的可靠性评估
根据 2021 年世界卫生组织脑肿瘤分类,即使没有微血管增生和/或坏死,含有 CDKN2A/B 基因同源缺失(HD)的星形细胞瘤也被定为 4 级。在这项研究中,我们旨在调查成人型 IDH 突变胶质瘤中 CDKN2A HD 与甲硫腺苷磷酸化酶(MTAP)表达缺失之间的关系,并评估 MTAP 免疫组织化学(IHC)作为 CDKN2A HD 替代生物标记物的敏感性和特异性以及观察者之间的一致性。研究人员选取了哈杰泰佩大学 2014 年至 2021 年期间确诊的 88 例星形细胞瘤和 71 例少突胶质细胞瘤病例,通过组织芯片进行 CDKN2A 荧光原位杂交和 MTAP IHC 检测。25例(15.7%)携带CDKN2A HD。第一观察者和第二观察者分别在 28 例(15.7%)和 27 例(17%)病例中检测到 MTAP 缺失。经计算,两名观察者检测 MTAP 的灵敏度和特异度分别为 88% 和 95.52%-96.27%。观察者之间的一致性非常好/完美(科恩卡帕系数 = 0.938)。在 4 个病例中观察到瘤内异质性。研究发现,MTAP IHC 是一种可靠的替代生物标记物,可作为 CDKN2A HD 鉴定的替代方法,具有较高的灵敏度和特异性,观察者之间的一致性也很高。
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CiteScore
7.20
自引率
4.30%
发文量
567
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