Lim Sun Min, Chang Hyun, Cha Yoon Jin, Liang Shile, Tai Yan Chin, Li Gu, Pestova Ekaterina, Policht Frank, Perez Thomas, Soo Ross A, Park Won Young, Kim Hye Ryun, Shim Hyo Sup, Cho Byoung Chul
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea.
Hematology and Medical Oncology, International St. Mary's Hospital, Catholic Kwandong University, College of Medicine, Incheon, Republic of Korea.
Lung Cancer. 2017 Sep;111:79-83. doi: 10.1016/j.lungcan.2017.07.016. Epub 2017 Jul 12.
ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib. Thus, it is clinically important to develop an effective screening strategy to detect patients who will benefit from such treatment. In this study, we aimed to validate analytical performance of Vysis ALK/ROS1 Dual Break Apart Probe Kit (RUO) in NSCLC.
Study population composed of three patient cohorts with histologically confirmed lung adenocarcinoma (patients with ALK rearrangement, patients with ROS1 rearrangement and patients with wild-type ALK and ROS1). Specimens consisted of 12 ALK-positive, 8 ROS1-positive and 21 ALK/ROS1-wild type formalin-fixed paraffin-embedded samples obtained from surgical resection or excisional biopsy. ALK rearrangement was previously assessed by Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular, Abbot Park, IL, USA) and ROS1 rearrangement was previously assessed by ZytoLight SPEC ROS1 Break Apart Probe (ZytoVision, GmbH). All specimens were re-evaluated by Vysis ALK/ROS1 Dual Break Apart Probe Kit. FISH images were scanned on BioView AllegroPlus system and interpreted via BioView SoloWeb remotely.
For a total of 41 patient samples, the concordance of the results by Vysis ALK/ROS1 Dual Break Apart Probe Kit was evaluated and compared to the known ALK and ROS1 rearrangement status of the specimen. Of the 12 ALK-positive cases, hybridization with Vysis ALK/ROS1 Dual Break Apart Probe Kit was successful in 10 cases (success rate 10/12, 83%) and of these 10 cases, all showed ALK rearrangement (100% concordance with the results of Vysis ALK Break Apart FISH Probe Kit). Two of the ALK+ cases were excluded due to weak ROS1 signals that could not be enumerated. Of the 8 ROS1-positive cases, 6 cases were successfully evaluated using Vysis ALK/ROS1 Dual Break Apart Probe Kit. The success rate was 75% (6/8), and of these 6 cases, all showed ROS1 rearrangement, giving a 100% concordance with ZytoLight SPEC ROS1 Break Apart Probe. Two of the cases were excluded due to weak ROS1 gold signal or high background. In the cohort of 21 wild-type cases, the success rate using Vysis ALK/ROS1 Dual Break Apart FISH Probe Kit was 85% (18/21) and the concordance with ALK and ROS1 probe kit was 100% (18/18).
Vysis ALK/ROS1 Dual Break Apart Probe Kit (RUO) can detect ALK and ROS1 rearrangement simultaneously in NSCLC.
ALK和ROS1基因重排是非小细胞肺癌（NSCLC）不同的分子亚群，它们是对ALK/ROS1抑制剂（如克唑替尼）反应的强预测生物标志物。因此，开发一种有效的筛查策略以检测将从此类治疗中获益的患者具有重要的临床意义。在本研究中，我们旨在验证Vysis ALK/ROS1双色分离探针试剂盒（研究用）在NSCLC中的分析性能。
研究人群由三个经组织学确诊为肺腺癌的患者队列组成（ALK重排患者、ROS1重排患者以及ALK和ROS1野生型患者）。样本包括12例ALK阳性、8例ROS1阳性以及21例ALK/ROS1野生型的福尔马林固定石蜡包埋样本，这些样本均取自手术切除或切除活检组织。ALK重排先前通过Vysis ALK双色分离FISH探针试剂盒（美国雅培分子公司，伊利诺伊州雅培公园）进行评估，ROS1重排先前通过ZytoLight SPEC ROS1双色分离探针（德国ZytoVision公司）进行评估。所有样本均使用Vysis ALK/ROS1双色分离探针试剂盒重新评估。FISH图像在BioView AllegroPlus系统上扫描，并通过BioView SoloWeb远程解读。
对于总共41例患者样本，评估了Vysis ALK/ROS1双色分离探针试剂盒结果的一致性，并与样本已知的ALK和ROS1重排状态进行比较。在12例ALK阳性病例中，Vysis ALK/ROS1双色分离探针试剂盒杂交成功10例（成功率10/12，83%），在这10例中，均显示ALK重排（与Vysis ALK双色分离FISH探针试剂盒结果100%一致）。2例ALK阳性病例因ROS1信号较弱无法计数而被排除。在8例ROS1阳性病例中，6例使用Vysis ALK/ROS1双色分离探针试剂盒成功评估。成功率为75%（6/8），在这6例中，均显示ROS1重排，与ZytoLight SPEC ROS1双色分离探针结果100%一致。2例病例因ROS1金信号较弱或背景较高而被排除。在21例野生型病例队列中，使用Vysis ALK/ROS1双色分离FISH探针试剂盒的成功率为85%（18/21），与ALK和ROS1探针试剂盒的一致性为100%（18/18）。
Vysis ALK/ROS1双色分离探针试剂盒（研究用）可在NSCLC中同时检测ALK和ROS1重排。
