ALK Status Testing in Non-Small Cell Lung Carcinoma Correlation Between Ultrasensitive IHC and FISH
ALK Status Testing in Non-Small Cell Lung Carcinoma Correlation Between Ultrasensitive IHC and FISH
复制标题
DOI：
10.1016/j.jmoldx.2013.01.004
复制
发表时间：
2013-05-01
影响因子：
4.1
通讯作者：
Tubbs, Raymond R.
中科院分区：
文献类型：
--
作者：
Minca, Eugen C.;Portier, Bryce P.;Tubbs, Raymond R.
晚期非小细胞肺癌(NSCLC)的ALK基因重排是克里佐替尼靶向治疗的一个指征。使用最近批准的体外诊断类FISH系统的荧光原位杂交(FISH)通常用于评估ALK状态。在非小细胞肺癌中，ALK融合转录本的低表达对更易接近的IHC构成了挑战。我们对296例晚期非小细胞肺癌患者的318例FFPE和40例匹配的ThinPrep标本进行了超灵敏的自动化IHC和FISH检测ALK状态的比较。在231份双信息样本中，IHC与FFPE-FISH有229份(31份阳性，198份阴性)，与ThinPrep-FISH的34份(5份阳性，29份阴性)符合。根据阴性的ThinPrep-FISH和与ALK阴性状态一致的临床数据，2例IHC阴性和FFPE-FISH交界性阳性的患者(分别为15%和18%)被重新分类为一致。总体而言，在包括ThinPrep-FISH和修正假阳性FFPE-FISH结果后，IHC对249例双重信息的NSCLC样本的ALK检测显示出100%的敏感性和特异性(95%CI，分别为0.86至1.00和0.97至1.00)。IHC比FFPE-FISH对更多的样本提供了更多的信息，揭示了更多的ALK阳性病例。与FISH的高度符合性保证了IHC作为非小细胞肺癌临床ALK检测算法方法的初始组成部分的常规使用，随后是IHC阳性病例的FISH确认。
ALK gene rearrangements in advanced non-small cell lung carcinomas (NSCLC) are an indication for targeted therapy with crizotinib. Fluorescence in situ hybridization (FISH) using a recently approved companion in vitro diagnostic class FISH system commonly assesses ALK status. More accessible IHC is challenged by low expression of ALK-fusion transcripts in NSCLC. We compared ultrasensitive automated IHC with FISH for detecting ALK status on 318 FFPE and 40 matched ThinPrep specimens from 296 patients with advanced NSCLC. IHC was concordant with FFPE-FISH on 229 of 231 dual-informative samples (31 positive and 198 negative) and with ThinPrep-FISH on 34 of 34 samples (5 positive and 29 negative). Two cases with negative IHC and borderline-positive FFPE-FISH (15% and 18%, respectively) were reclassified as concordant based on negative matched ThinPrep-FISH and clinical data consistent with ALK-negative status. Overall, after including ThinPrep-FISH and amending the falsepositive FFPE-FISH results, IHC demonstrated 100% sensitivity and specificity (95% CI, 0.86 to 1.00 and 0.97 to 1.00, respectively) for ALK detection on 249 dual-informative NSCLC samples. IHC was informative on significantly more samples than FFPE-FISH, revealing additional ALK-positive cases. The high concordance with FISH warrants IHC's routine use as the initial component of an algorithmic approach to clinical ALK testing in NSCLC, followed by reflex FISH confirmation of IHC-positive cases.