Chen Lin1, Xun Shi1, Shao Yang2, Jun Zhao1, Qiong He1, Ying Jin3, Xinmin Yu4. 1. Department of Medical Oncology, Zhejiang Cancer Hospital, China. 2. Nanjing Geneseeq Technology Inc., Nangjing, China. 3. Department of Medical Oncology, Zhejiang Cancer Hospital, China; Zhejiang Key Laboratory of Radiation Oncology, China. Electronic address: jinying@zjcc.org.cn. 4. Department of Medical Oncology, Zhejiang Cancer Hospital, China; Zhejiang Key Laboratory of Diagnosis and Treatment Technology of Thoracic Oncology, China. Electronic address: yuxm@zjcc.org.cn.
Abstract
PURPOSE: Anaplastic lymphoma kinase (ALK) is now a validated kinase target in non-small cell lung cancer (NSCLC). We implemented three ALK laboratory methodologies: fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and next-generation sequencing (NGS) to detect EML4-ALK fusions and compared the predictive value for Crizotinib efficacy in ALK-positive patients. METHODS: 55 ALK positive patients confirmed by at least one method were enrolled in the present study, of whom 45 cases were assessed by FISH, IHC and NGS concurrently, and another 10 cases only received IHC and NGS assessment for ALK status. RESULTS: IHC presented the uppermost positive rate (94.5%), followed by NGS (92.7%) and FISH(82.4%), among which IHC and NGS had the highest concordance rate of 87.3%. No difference was detected in ORR, DCR and PFS of ALK positive cases defined in three groups. Notably, NGS positive patients were correlated with a higher DCR and longer PFS compared to NGS negative cases (P = 0.02 and P = 0.09), while FISH and IHC status were not distinguishing in predicting the outcome of Crizotinib. TP53 concurrent mutation might reduce responsiveness to Crizotinib and worsen prognosis in ALK-rearranged NSCLC. CONCLUSION: FISH present a certain false-negative rate although considered the gold standard. Ventana-D5F3 IHC is qualified as a screening tool, while NGS positive may predict clinical benefit of Crizotinib more accurately, allowing efficient test for specific variants and concurrent genomic alterations.
PURPOSE:Anaplastic lymphoma kinase (ALK) is now a validated kinase target in non-small cell lung cancer (NSCLC). We implemented three ALK laboratory methodologies: fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and next-generation sequencing (NGS) to detect EML4-ALK fusions and compared the predictive value for Crizotinib efficacy in ALK-positive patients. METHODS: 55 ALK positive patients confirmed by at least one method were enrolled in the present study, of whom 45 cases were assessed by FISH, IHC and NGS concurrently, and another 10 cases only received IHC and NGS assessment for ALK status. RESULTS: IHC presented the uppermost positive rate (94.5%), followed by NGS (92.7%) and FISH(82.4%), among which IHC and NGS had the highest concordance rate of 87.3%. No difference was detected in ORR, DCR and PFS of ALK positive cases defined in three groups. Notably, NGS positive patients were correlated with a higher DCR and longer PFS compared to NGS negative cases (P = 0.02 and P = 0.09), while FISH and IHC status were not distinguishing in predicting the outcome of Crizotinib. TP53 concurrent mutation might reduce responsiveness to Crizotinib and worsen prognosis in ALK-rearranged NSCLC. CONCLUSION: FISH present a certain false-negative rate although considered the gold standard. Ventana-D5F3 IHC is qualified as a screening tool, while NGS positive may predict clinical benefit of Crizotinib more accurately, allowing efficient test for specific variants and concurrent genomic alterations.
Authors: Matteo Canale; Luigi Pasini; Giuseppe Bronte; Angelo Delmonte; Paola Cravero; Lucio Crinò; Paola Ulivi Journal: Transl Lung Cancer Res Date: 2019-11
Authors: Sebastian Mondaca; Emily S Lebow; Azadeh Namakydoust; Pedram Razavi; Jorge S Reis-Filho; Ronglai Shen; Michael Offin; Hai-Yan Tu; Yonina Murciano-Goroff; Chongrui Xu; Alex Makhnin; Andres Martinez; Nick Pavlakis; Stephen Clarke; Malinda Itchins; Adrian Lee; Andreas Rimner; Daniel Gomez; Gaetano Rocco; Jamie E Chaft; Gregory J Riely; Charles M Rudin; David R Jones; Mark Li; Tristan Shaffer; Seyed Ali Hosseini; Caterina Bertucci; Lee P Lim; Alexander Drilon; Michael F Berger; Ryma Benayed; Maria E Arcila; James M Isbell; Bob T Li Journal: Lung Cancer Date: 2021-07-17 Impact factor: 6.081