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.

中文翻译：

---

甲硫腺苷磷酸化酶免疫组织化学作为成人型 IDH 突变弥漫性胶质瘤中 CDKN2A 纯合缺失替代生物标志物的可靠性评估

根据 2021 年世界卫生组织脑肿瘤分类，即使不存在微血管增殖和/或坏死，含有 CDKN2A/B 纯合缺失 (HD) 的星形细胞瘤也被指定为 4 级。在本研究中，我们旨在研究成人型 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) 的敏感性和特异性以及观察者间一致性作为替代指标CDKN2A HD 的生物标志物。选择Hacettepe大学2014年至2021年间诊断的88例星形细胞瘤和71例少突胶质细胞瘤病例，利用组织芯片进行CDKN2A荧光原位杂交和MTAP IHC。25 例 (15.7%) 病例携带 CDKN2A HD。第一位观察者检测到 28 例 (15.7%) MTAP 丢失，第二位观察者检测到 27 例 (17%) MTAP 丢失。对于 2 名观察者，MTAP 的敏感性和特异性计算为 88% 和 95.52%-96.27%。观察者之间注意到非常好的/完美的一致性（科恩卡帕系数 = 0.938）。4例观察到瘤内异质性。MTAP IHC 被发现是一种可靠的替代生物标志物，可以替代 CDKN2A HD 鉴定，具有高灵敏度和特异性以及高观察者间一致性。