Ahn Bokyung, Jang Se Jin, Hwang Hee Sang
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Am J Clin Pathol. 2025 Feb 12;163(2):258-265. doi: 10.1093/ajcp/aqae118.
ROS-1 immunohistochemistry (IHC) is a common method for screening ROS1 fusion in the clinical management of non-small cell lung cancer. The interpretation criteria for ROS-1 SP384 IHC, however, remain unestablished.
Sixty-five non-small cell lung cancer cases underwent AmoyDx ROS1 fusion real-time polymerase chain reaction (PCR) study and ROS-1 SP384 IHC tests, which were retrieved for analysis. ROS-1 IHC tests were interpreted based on the established classifiers as well as the presence of diffuse homogeneous immunoreactivity. The diagnostic accuracies of these ROS-1 IHC interpretation methods were evaluated by comparing them with the ROS1 real-time PCR results.
Previous ROS-1 IHC classifiers demonstrated high sensitivity for positive ROS1 real-time PCR results (100%), but they showed low specificities (25%-50%) and overall accuracies (58%-72%). In contrast, the diffuse homogeneous ROS-1 immunoreactivity predicted positive ROS1 real-time PCR results with much higher specificity (94%) and overall accuracy (95%), albeit with a slightly lower sensitivity (97%). Some cases that showed discrepancy between diffuse homogeneous ROS-1 immunoreactivity and real-time PCR results involved rare ROS1::LDLR fusion and suboptimal IHC staining.
A 3-tier reporting system for ROS-1 SP384 IHC testing combining previous interpretation criteria and diffuse and homogeneous immunoreactivity may better predict ROS1 fusion status without decreasing specificity.
ROS-1免疫组化（IHC）是在非小细胞肺癌临床管理中筛查ROS1融合的常用方法。然而，ROS-1 SP384 IHC的判读标准尚未确立。
对65例非小细胞肺癌病例进行了厦门艾德ROS1融合实时聚合酶链反应（PCR）研究及ROS-1 SP384 IHC检测，并对结果进行分析。ROS-1 IHC检测根据既定的分类标准以及弥漫性均匀免疫反应性进行判读。通过与ROS1实时PCR结果比较，评估这些ROS-1 IHC判读方法的诊断准确性。
既往的ROS-1 IHC分类标准对ROS1实时PCR阳性结果显示出高敏感性（100%），但特异性较低（25%-50%），总体准确性也较低（58%-72%）。相比之下，弥漫性均匀的ROS-1免疫反应性对ROS1实时PCR阳性结果的预测具有更高的特异性（94%）和总体准确性（95%），尽管敏感性略低（97%）。一些弥漫性均匀的ROS-1免疫反应性与实时PCR结果存在差异的病例涉及罕见的ROS1::LDLR融合和IHC染色欠佳。
结合既往判读标准以及弥漫性均匀免疫反应性的ROS-1 SP384 IHC检测三层报告系统，可能在不降低特异性的情况下更好地预测ROS1融合状态。
