Clinical Research Papers:
Responses to crizotinib in patients with ALK-positive lung adenocarcinoma who tested immunohistochemistry (IHC)-positive and fluorescence in situ hybridization (FISH)-negative
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Di Ma1,*, Zheng Wang2,*, Lin Yang3, Xinlin Mu4, Yan Wang1, Xinming Zhao5, Junling Li1, Dongmei Lin6
1Department of Medical Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing, China
2Department of Pathology, Beijing Hospital of the Ministry of Health, Beijing, China
3Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing, China
4Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, China
5Department of Diagnostic Radiology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing, China
6Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
*These authors have contributed equally to this work
Junling Li, email: [email protected]
Dongmei Lin, email: [email protected]
Keywords: non-small-cell lung cancer, ALK status, crizotinib, immunohistochemistry, fluorescence in situ hybridization
Received: September 21, 2015 Accepted: June 29, 2016 Published: July 13, 2016
Although the Ventana immunohistochemistry (IHC) platform for detecting anaplastic lymphoma kinase gene (ALK) (D5F3) expression was recently approved by the US Food and Drugs Administration (FDA), fluorescence in situ hybridization (FISH) is still the “gold-standard” method recommended by the US National Comprehensive Cancer Network (NCCN) guideline for NSCLC. We evaluated 6 ALK-positive lung adenocarcinoma patients who tested Ventana IHC-positive and FISH-negative and assessed their clinical responses to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Histologic and cytologic specimens from the 6 patients were stained with Ventana anti-ALK(D5F3) rabbit monoclonal primary antibody using the OptiView™ DAB IHC detection kit and OptiView™ amplification kit on a Ventana BenchMark XT processor. In addition, they were also tested by FISH, qRT-PCR, next-generation sequencing (NGS), and RNAscope ISH analysis. All patients received crizotinib treatment and their follow-up clinical data were recorded. The objective response rate achieved with crizotinib therapy was 66.7% (4/6 partial responses and 2/6 stable disease). One patient in whom a new fusion type (EML4->EXOC6B->ALK fusion) was identified obtained a partial response. These findings indicate that patients with ALK-positive lung adenocarcinoma who test Ventana IHC-positive and FISH-negative may still respond to crizotinib therapy.
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