Ancillary studies facilitate accurate diagnosis of morphologically challenging mesothelial proliferations. The current diagnostic algorithm proceeds from BAP1 immunohistochemistry to CDKN2A fluorescence in situ hybridization. While MTAP immunohistochemistry has recently shown promise as a surrogate for CDKN2A fluorescence in situ hybridization, it has been examined in only a few single-institution studies. Furthermore, there are no published reports on interobserver agreement or interlaboratory reproducibility for MTAP immunohistochemistry. We performed MTAP immunohistochemistry on 20 benign mesothelial lesions and 99 malignant mesotheliomas from five mesothelioma centers in four countries, and each MTAP stain was independently interpreted by four pathologists. CDKN2A fluorescence in situ hybridization data were available for a subset of cases, and a subset of cases was subjected in MTAP immunohistochemistry in multiple laboratories to assess interlaboratory reproducibility. Interobserver agreement in MTAP immunostain interpretation was excellent for all mesothelial lesions (kappa: 0.85) and for malignant mesothelioma cases only (kappa: 0.82). Interlaboratory reproducibility was also excellent (kappa values for paired protocols: 0.77-0.89). MTAP loss by immunohistochemistry was 78% sensitive and 96% specific for CDKN2A homozygous deletion. MTAP immunohistochemistry is a reliable surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant mesothelioma. Interobserver agreement is excellent for interpretation of MTAP staining, and protocols performed in different laboratories yield concordant MTAP staining results. Rare cases with immunohistochemical MTAP loss may retain normal CDKN2A copy number, and the MTAP staining results should be correlated with clinicopathologic findings and other ancillary studies.

中文翻译：

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MTAP 免疫组织化学是 CDKN2A 荧光原位杂交诊断恶性胸膜间皮瘤的一种准确且可重复的替代方法。

辅助研究有助于准确诊断形态学上具有挑战性的间皮增生。目前的诊断算法从 BAP1 免疫组织化学发展到 CDKN2A 荧光原位杂交。虽然 MTAP 免疫组织化学最近显示出有望作为 CDKN2A 荧光原位杂交的替代物，但仅在少数单一机构研究中对其进行了检查。此外，还没有关于 MTAP 免疫组织化学的观察者间协议或实验室间再现性的已发表报告。我们对来自四个国家的五个间皮瘤中心的 20 个良性间皮病变和 99 个恶性间皮瘤进行了 MTAP 免疫组织化学，每个 MTAP 染色由四位病理学家独立解释。部分病例可获得 CDKN2A 荧光原位杂交数据，一部分病例在多个实验室进行了 MTAP 免疫组织化学检测，以评估实验室间的可重复性。MTAP 免疫染色解释中的观察者间协议对于所有间皮病变 (kappa: 0.85) 和仅恶性间皮瘤病例 (kappa: 0.82) 都非常好。实验室间的重现性也非常好（配对方案的 kappa 值：0.77-0.89）。免疫组织化学检测的 MTAP 丢失对 CDKN2A 纯合缺失的敏感性为 78%，特异性为 96%。MTAP 免疫组织化学是 CDKN2A 荧光原位杂交诊断恶性间皮瘤的可靠替代方法。观察者之间的一致性非常适合解释 MTAP 染色，并且在不同实验室执行的方案会产生一致的 MTAP 染色结果。