文章：

通过拷贝数变异阵列检测到的CDKN2A和MTAP基因缺失与胸膜间皮瘤中p16和MTAP蛋白的缺失相关

Deletions ofCDKN2AandMTAPDetected by Copy-Number Variation Array Are Associated with Loss of p16 and MTAP Protein in Pleural Mesothelioma

原文发布日期：13 October 2023

DOI: 10.3390/cancers15204978

类型: Article

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英文摘要：

CDKN2Adeletion is a common alteration in pleural mesothelioma (PM) and frequently associated with co-deletion ofMTAP. Since the standard detection method forCDKN2Adeletion and FISH analysis is relatively expensive, we here investigated the suitability of inexpensive p16 and MTAP IHC by comparing concordance between IHC and OncoScan CNV arrays on samples from 52 PM patients. Concordance was determined using Cohen’s kappa statistics. Loss ofCDKN2Awas associated with co-deletion ofMTAPin 71% of cases.CDKN2A-MTAPcopy-number normal cases were also IHC positive in 93% of cases for p16 and 100% for MTAP, while homozygous deletion ofCDKN2A-MTAPwas always associated with negative IHC for both proteins. In cases with heterozygousCDKN2A-MTAPloss, IHC expression of p16 and MTAP was negative in 100% and 71%, respectively. MTAP and p16 IHC showed high sensitivity (MTAP 86.5%, p16 100%) and specificity (MTAP 100%, p16 93.3%) for the detection of any gene loss. Loss of MTAP expression occurred exclusively in conjunction with loss of p16 labeling. Both p16 and MTAP IHC showed high concordance with Oncoscan CNV arrays (kappa = 0.952,p< 0.0001, and kappa = 0.787,p< 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM.

摘要翻译： 

CDKN2A缺失是胸膜间皮瘤（PM）中常见的基因改变，常伴随MTAP的共缺失。由于检测CDKN2A缺失的标准方法——荧光原位杂交（FISH）分析成本较高，本研究通过比较52例PM患者样本的免疫组化（IHC）与OncoScan拷贝数变异（CNV）芯片检测结果，评估了成本较低的p16和MTAP免疫组化检测的适用性。一致性分析采用Cohen's kappa统计方法。结果显示，71%的病例中CDKN2A缺失与MTAP共缺失相关。在CDKN2A-MTAP拷贝数正常的病例中，p16和MTAP免疫组化阳性率分别为93%和100%；而CDKN2A-MTAP纯合缺失病例的两种蛋白免疫组化检测结果均为阴性。对于CDKN2A-MTAP杂合缺失病例，p16和MTAP免疫组化阴性率分别为100%和71%。MTAP和p16免疫组化检测基因缺失具有高敏感性（MTAP 86.5%，p16 100%）和高特异性（MTAP 100%，p16 93.3%）。MTAP表达缺失仅与p16标记缺失同时发生。p16和MTAP免疫组化与Oncoscan CNV芯片检测结果均呈现高度一致性（kappa值分别为0.952和0.787，p值均<0.0001）。我们推荐联合使用MTAP和p16免疫组化检测以辅助胸膜间皮瘤的诊断。

原文链接：

Deletions ofCDKN2AandMTAPDetected by Copy-Number Variation Array Are Associated with Loss of p16 and MTAP Protein in Pleural Mesothelioma