Wang S N, Wang W, Zhang X W, Zhang Y Q, Xiong Y L, Liu L, Teng L H
Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Zhonghua Bing Li Xue Za Zhi. 2024 May 8;53(5):439-445. doi: 10.3760/cma.j.cn112151-20230815-00069.
To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors. 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. 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 (<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas (<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA (<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. 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.
为了研究甲硫腺苷磷酸化酶（MTAP）和p16的免疫组织化学是否可用于预测各种脑肿瘤中的CDKN2A状态。收集并分析了2017年11月至2023年10月在中国北京首都医科大学宣武医院诊断的118例异柠檬酸脱氢酶（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（PXA）和20例脑膜瘤。通过荧光原位杂交或二代测序检测CDKN2A状态。用免疫组织化学检测MTAP和p16蛋白的表达。检测MTAP/p16表达缺失与CDKN2A纯合/杂合缺失的相关性。在118例IDH突变型星形细胞瘤中，13例显示CDKN2A纯合缺失。所有这些病例均无MTAP表达，而9例无p16表达。在16例IDH野生型胶质母细胞瘤中，6例显示CDKN2A纯合缺失。所有6例均无MTAP表达，其中3例无p16表达。在17例PXA病例中，4例显示CDKN2A纯合缺失，这4例中MTAP和p16的表达也缺失。在20例脑膜瘤中，4例显示CDKN2A纯合缺失。它们的MTAP和p16表达也缺失。在四种类型的脑肿瘤中，MTAP与CDKN2A纯合缺失显著相关（<0.05），敏感性为100%。然而，它仅与星形细胞瘤中CDKN2A杂合性缺失（LOH）显著相关（<0.001）。P16与IDH突变型星形细胞瘤和PXA中的CDKN2A纯合缺失相关（<0.001），但与CDKN2A的LOH无关。其敏感性和特异性低于MTAP。MTAP可作为成人IDH突变型星形细胞瘤、PXA、成人IDH野生型胶质母细胞瘤和脑膜瘤中CDKN2A纯合缺失的预测替代指标。然而，p16仅可用于前两种肿瘤类型，其特异性和敏感性低于MTAP。
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