RESUMO
BACKGROUND: The c-mesenchymal-epithelial transition factor (C-MET) is an oncogene encoding a tyrosine kinase receptor that plays an important role in tumor growth and metastasis. The National Comprehensive Cancer Network (NCCN) guidelines have approved carbatinib/crizotinib for advanced non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping. METHODS: In June 2020, the Department of Respiratory and Critical Care Medicine of Peking University People's Hospital admitted a 72-year-old male patient with lung adenocarcinoma (LADC) with a history of interstitial lung disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis. Genetic examination by next-generation sequencing showed an intergenic fusion of MET, and crizotinib was administered on August 14, 2020. Follow-up showed that tumor volume was significantly reduced. However, crizotinib was discontinued in November 2020 because of the patient's worsening interstitial lung disease, and CT scans showed continued partial response (PR) for 5 months. In April 2021, right lower lobe mass progressed, and disease progression was considered. CONCLUSION: This was the first case of a patient with LADC with MET intergenic fusion who significantly benefited from crizotinib. Even after crizotinib was discontinued for 5 months, the patient continued exhibiting PR, suggesting that MET intergenic fusion may have carcinogenic activity in LADC and was sensitive to crizotinib.
RESUMO
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.