Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
Virchows Arch. 2013 Oct;463(4):583-91. doi: 10.1007/s00428-013-1472-7. Epub 2013 Aug 18.
Accurate determination of anaplastic lymphoma kinase (ALK) rearrangements is critical in identifying ALK-positive patients for targeted therapy in non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the current standard method to detect ALK rearrangements but is technically challenging and costly. We compared optimised immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization techniques in this study of 139 samples of advanced NSCLC with non-squamous histology. ALK alteration was found in 32.6 % (43/132) of patients by FISH, 32.9 % (45/137) of patients by IHC and 27.9 % (34/122) of samples by qRT-PCR (concordance rate of 96.9 % between FISH and IHC, 95.7 % between FISH and qRT-PCR, P < 0.001). IHC sensitivity and specificity were 97.7 % and 96.6 %, respectively, while the sensitivity and specificity of qRT-PCR were 89.2 % and 98.7 %, respectively. ALK rearrangements were more common in young patients (P = 0.007), non-smokers or light smokers (P = 0.008) and adenocarcinoma histology, especially with signet ring cell features (P < 0.001). Optimised IHC could be a useful method in screening ALK rearrangements in clinical practice with qRT-PCR as an alternative diagnostic tool to clarify specific ALK variants.
准确确定间变性淋巴瘤激酶 (ALK) 重排对于确定非小细胞肺癌 (NSCLC) 中ALK 阳性患者的靶向治疗至关重要。荧光原位杂交 (FISH) 是目前检测 ALK 重排的标准方法，但技术上具有挑战性且成本高昂。在这项针对非鳞状组织学的 139 例晚期 NSCLC 样本的研究中，我们比较了优化的免疫组织化学 (IHC)、实时定量聚合酶链反应 (qRT-PCR) 和荧光原位杂交技术。通过 FISH 在 32.6%（43/132）的患者中发现 ALK 改变，在 32.9%（45/137）的患者中通过 IHC 发现 ALK 改变，在 27.9%（34/122）的样本中通过 qRT-PCR 发现 ALK 改变（FISH 与 IHC 的一致性率为 96.9%，FISH 与 qRT-PCR 的一致性率为 95.7%，P<0.001）。IHC 的敏感性和特异性分别为 97.7%和 96.6%，而 qRT-PCR 的敏感性和特异性分别为 89.2%和 98.7%。ALK 重排更常见于年轻患者（P=0.007）、非吸烟者或轻度吸烟者（P=0.008）和腺癌组织学，尤其是具有印戒细胞特征的腺癌（P<0.001）。优化的 IHC 可能是一种在临床实践中筛选 ALK 重排的有用方法，qRT-PCR 可作为澄清特定 ALK 变体的替代诊断工具。
