Vrugt Bart, Kirschner Michaela B, Meerang Mayura, Oehl Kathrin, Wagner Ulrich, Soltermann Alex, Moch Holger, Opitz Isabelle, Wild Peter J
Institute of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.
Department of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, Switzerland.
Cancers (Basel). 2023 Oct 13;15(20):4978. doi: 10.3390/cancers15204978.
deletion is a common alteration in pleural mesothelioma (PM) and frequently associated with co-deletion of . Since the standard detection method for deletion 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 of was associated with co-deletion of in 71% of cases. copy-number normal cases were also IHC positive in 93% of cases for p16 and 100% for MTAP, while homozygous deletion of was always associated with negative IHC for both proteins. In cases with heterozygous loss, 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, < 0.0001, and kappa = 0.787, < 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM.
缺失是胸膜间皮瘤（PM）中常见的改变，且常与……的共同缺失相关。由于用于……缺失检测的标准方法和荧光原位杂交（FISH）分析相对昂贵，我们在此通过比较52例PM患者样本的免疫组化（IHC）与OncoScan拷贝数变异（CNV）阵列之间的一致性，研究了廉价的p16和MTAP免疫组化的适用性。使用科恩kappa统计量确定一致性。在71%的病例中，……的缺失与……的共同缺失相关。……拷贝数正常的病例中，93%的p16病例和100%的MTAP病例免疫组化也呈阳性，而……的纯合缺失总是与这两种蛋白的免疫组化阴性相关。在杂合性……缺失的病例中，p16和MTAP的免疫组化表达分别在100%和71%的病例中为阴性。MTAP和p16免疫组化在检测任何基因缺失方面显示出高灵敏度（MTAP为86.5%，p16为100%）和特异性（MTAP为100%，p16为93.3%）。MTAP表达的缺失仅与p16标记的缺失同时出现。p16和MTAP免疫组化与Oncoscan CNV阵列均显示出高度一致性（kappa分别为0.952，P<0.0001和kappa为0.787，P<0.0001）。我们建议联合使用MTAP和p16免疫组化来确诊PM。
