Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China.
Cancer Commun (Lond). 2024 Sep;44(9):992-1004. doi: 10.1002/cac2.12593. Epub 2024 Jul 17.
Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.
In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.
The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05).
This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.
在晚期非小细胞肺癌（NSCLC）中进行间变性淋巴瘤激酶（ALK）检测可以帮助医生为携带 ALK 基因重排的患者提供靶向治疗。本研究旨在调查晚期 NSCLC 中 ALK 基因重排的真实世界检测模式和阳性率。
在这项真实世界的研究（ChiCTR2000030266）中，回顾性分析了 2018 年 10 月 1 日至 2019 年 12 月 31 日期间在中国 30 家医疗中心接受 ALK 重排检测的 23689 例晚期 NSCLC 患者和 17436 例晚期肺腺癌患者。在研究开始前进行了解释性培训。在参与中心使用免疫组织化学（IHC）-VENTANA-D5F3 进行质量控制。计算了阳性 ALK 基因重排率和一致性率。还研究了 ALK 基因重排与临床病理特征的相关性。
23689 例晚期 NSCLC 患者中 ALK 基因总重排率为 6.7%，17436 例晚期肺腺癌患者中 ALK 基因重排率为 8.2%。IHC-VENTANA-D5F3 的质量控制分析显示，院内一致性率为 98.2%（879/895），院间一致性率为 99.2%（646/651）。IHC-VENTANA-D5F3 用于 53.6%的腺癌亚组，实时聚合酶链反应（RT-PCR）用于 25.4%，下一代测序（NGS）用于 18.3%，荧光原位杂交（FISH）用于 15.9%。对于用多种方法检测的标本，IHC-VENTANA-D5F3 确认的一致性率为 FISH 为 98.0%（822/839），NGS 为 98.7%（1222/1238），RT-PCR 为 91.3%（146/160）。在总 NSCLC 人群和腺癌亚组中，女性、≤35 岁、从不吸烟、肿瘤细胞密度>50%和转移性标本用于检测的 ALK 基因总重排率较高（均 P<0.05）。
本研究强调了晚期 NSCLC 中 ALK 检测的真实世界变异性和挑战，表明在 ALK 阳性患者中主要使用 IHC-VENTANA-D5F3，一致性高，具有明显的临床病理特征。这些发现强调了需要就最佳检测实践达成共识，并支持制定精细的 ALK 检测策略，以提高 NSCLC 的诊断准确性和治疗决策。
