Ozkizilkaya Hanim I, Vinocha Anjali, Dono Antonio, Ogunbona Oluwaseun Basit, Toruner Gokce A, Aung Phyu P, Kamiya Matsuoka Carlos, Esquenazi Yoshua, DeMonte Franco, Ballester Leomar Y
Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Vivian L. Smith Department of Neurosurgery, The University of Texas, Health Science Center at Houston, Houston, TX 77030, USA.
Cancers (Basel). 2024 Sep 27;16(19):3299. doi: 10.3390/cancers16193299.
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.
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, FISH was utilized as the gold standard.
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 homozygous loss by FISH also showed loss of MTAP expression by IHC. One grade 2 meningioma showed regional loss 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.
P16 expression was variable and did not correlate with either MTAP expression or FISH results. MTAP IHC is a promising surrogate marker for the evaluation of status in meningiomas.
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指定为世界卫生组织（WHO）3级中枢神经系统（CNS）肿瘤的参数之一。通过测序或荧光原位杂交（FISH）评估CDKN2A/B成本高昂，且并非总能轻易获得。基于免疫组织化学（IHC）的用于评估CDKN2A/B缺失的标志物将以更低的成本提供更快的结果。
这项回顾性研究纳入了2016年至2019年间在我们机构被诊断为脑膜瘤的患者。使用存档的肿瘤组织进行分析。使用两种不同抗体在不同稀释度（1:1200、1:400、1:200、1:100）下进行甲基硫代腺苷磷酸化酶（MTAP）免疫组织化学（IHC），并同时进行p16 IHC。这些分析在两个不同机构进行。为了确定MTAP和p16作为CDKN2A/B缺失替代标志物的敏感性和特异性，将FISH用作金标准。
总体而言，在机构1中，46/49个肿瘤显示MTAP强染色（94%），在机构2中，44/49（90%）显示弱阳性或阳性结果。1例通过FISH显示纯合缺失的3级脑膜瘤通过IHC也显示MTAP表达缺失。1例2级脑膜瘤通过FISH显示区域缺失，在不同IHC条件下MTAP表达可变。使用Abnova抗MTAP单克隆抗体在1:100稀释度下进行MTAP表达评估效果更佳。
p16表达可变，与MTAP表达或FISH结果均无相关性。MTAP IHC是评估脑膜瘤中CDKN2A/B状态的有前景的替代标志物。
