Background: Homozygous cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss is one of the parameters that support the designation of meningiomas as Central Nervous System (CNS) WHO grade 3 tumors. Evaluation of CDKN2A/B by sequencing or Fluorescence in situ hybridization (FISH) is costly and not always readily accessible. An immunohistochemistry (IHC)-based marker for the evaluation of CDKN2A/B loss would provide faster results at a lower cost. Methods: This retrospective study included patients diagnosed with meningioma at our institution between 2016 and 2019. Archival tumor tissue was used for analysis. MTAP immunohistochemistry (IHC) was performed at various dilutions (1:1200, 1:400, 1:200, 1:100) using two different antibodies, and p16 IHC was conducted simultaneously. These analyses were carried out at two different institutions. To determine the sensitivity and specificity of MTAP and p16 as surrogate markers for CDKN2A/B loss,CDKN2AFISH was utilized as the gold standard. Results: Overall, 46/49 tumors showed strong MTAP staining (94%) at institution 1, and 44/49 (90%) showed either faint positive or positive results at institution 2. One grade 3 meningioma that demonstrated homozygousCDKN2Aloss by FISH also showed loss of MTAP expression by IHC. One grade 2 meningioma showed regionalCDKN2Aloss by FISH and variable MTAP expression under different IHC conditions. MTAP expression evaluation was superior at a dilution of 1:100 with the Abnova Anti-MTAP Monoclonal antibody. Conclusions: P16 expression was variable and did not correlate with either MTAP expression orCDKN2AFISH results. MTAP IHC is a promising surrogate marker for the evaluation ofCDKN2Astatus in meningiomas.
背景：纯合性细胞周期蛋白依赖性激酶抑制剂2A/B（CDKN2A/B）缺失是支持将脑膜瘤归类为中枢神经系统（CNS）WHO 3级肿瘤的指标之一。通过测序或荧光原位杂交（FISH）评估CDKN2A/B成本较高且不易普及。基于免疫组织化学（IHC）的标记物检测CDKN2A/B缺失能够以更低成本快速获得结果。方法：本回顾性研究纳入了2016年至2019年间在我院诊断为脑膜瘤的患者，使用存档肿瘤组织进行分析。采用两种不同抗体在不同稀释度（1:1200、1:400、1:200、1:100）下进行MTAP免疫组化检测，并同步开展p16免疫组化分析，相关检测在两个独立机构完成。以CDKN2A FISH作为金标准，评估MTAP和p16作为CDKN2A/B缺失替代标记物的敏感性与特异性。结果：总体而言，机构1中46/49例肿瘤（94%）显示强MTAP染色，机构2中44/49例（90%）呈弱阳性或阳性表达。一例经FISH证实存在纯合性CDKN2A缺失的3级脑膜瘤，其IHC检测同时显示MTAP表达缺失；另一例2级脑膜瘤经FISH检测显示区域性CDKN2A缺失，在不同IHC条件下呈现MTAP表达异质性。使用Abnova抗MTAP单克隆抗体在1:100稀释度下进行MTAP表达评估效果最佳。结论：p16表达存在异质性，与MTAP表达及CDKN2A FISH结果均无相关性。MTAP免疫组化检测有望成为评估脑膜瘤CDKN2A状态的替代标记物。
MTAP and p16 IHC as Markers for CDKN2A/B Loss in Meningiomas
肿瘤(癌症)患者之家