摘要目的:探索在多种脑肿瘤中应用甲硫腺苷磷酸化酶（methylthioadenosine phosphorylase，MTAP）与p16免疫组织化学染色预测CDKN2A基因状态的可行性。方法:收集2017年11月至2023年10月首都医科大学宣武医院118例IDH突变型星形细胞瘤、16例IDH野生型胶质母细胞瘤、17例多形性黄色星形细胞瘤（pleomorphic xanthoastrocytoma，PXA）及20例脑膜瘤标本（共171例标本）进行回顾性分析，采用荧光原位杂交及二代测序技术检测CDKN2A基因状态，免疫组织化学方法检测MTAP及p16蛋白的表达情况，统计分析MTAP及p16蛋白缺失与CDKN2A纯合性/杂合性缺失的一致性。结果:118例IDH突变型星形细胞瘤中13例存在CDKN2A纯合性缺失，同时，这13例MTAP表达均缺失，其中9例存在p16表达缺失；16例IDH野生型胶质母细胞瘤中6例存在CDKN2A纯合性缺失，这6例MTAP表达缺失，其中3例存在p16表达缺失；17例PXA中4例存在CDKN2A纯合性缺失，这4例MTAP及p16表达均缺失；20例脑膜瘤中4例存在CDKN2A纯合性缺失，这4例MTAP及p16表达均缺失。经统计分析，在4类脑肿瘤中，MTAP均与CDKN2A纯合性缺失显著相关（ P<0.05），灵敏度均达100%，但其与CDKN2A杂合性缺失仅在星形细胞瘤中显著相关（ P<0.001）。p16与CDKN2A纯合性缺失在IDH突变型星形细胞瘤及PXA中具有显著相关性（ P<0.001），与CDKN2A的杂合性缺失无相关性，但其灵敏度及特异度均不及MTAP。 结论:MTAP在成人型IDH突变型星形细胞瘤、PXA、成人型IDH野生型胶质母细胞瘤及脑膜瘤中能够作为CDKN2A纯合性缺失的预筛手段，而p16仅能在前两者肿瘤中作为预筛指标，且特异度及灵敏度均不及MTAP。

abstractsObjective:To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors.Methods:A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined.Results:Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion ( P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas ( P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA ( P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions:MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.