Responses to crizotinib in patients with ALK-positive lung adenocarcinoma who tested immunohistochemistry (IHC)-positive and fluorescence in situ hybridization (FISH)-negative

Autor: Junling Li, Wang Zheng, Lin Yang, Xinming Zhao, Yan Wang, Xinlin Mu, Dongmei Lin, Di Ma
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Pathology
Lung Neoplasms
Time Factors
Oncogene Proteins
Fusion

Pyridines
Tyrosine-kinase inhibitor
0302 clinical medicine
hemic and lymphatic diseases
Anaplastic lymphoma kinase
Anaplastic Lymphoma Kinase
Precision Medicine
In Situ Hybridization
Fluorescence

medicine.diagnostic_test
ALK status
Middle Aged
Immunohistochemistry
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Monoclonal
Adenocarcinoma
Female
medicine.drug
Adult
China
medicine.medical_specialty
medicine.drug_class
Adenocarcinoma of Lung
Antineoplastic Agents
03 medical and health sciences
Crizotinib
Predictive Value of Tests
Biomarkers
Tumor

medicine
Humans
Protein Kinase Inhibitors
fluorescence in situ hybridization
Aged
business.industry
Patient Selection
Receptor Protein-Tyrosine Kinases
Cancer
medicine.disease
030104 developmental biology
non-small-cell lung cancer
Cancer research
Pyrazoles
Clinical Research Paper
Tomography
X-Ray Computed

business
Fluorescence in situ hybridization
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: 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.
Databáze: OpenAIRE