Abstract
To investigate the use of molecular testing on cytological specimens in selecting advanced non-small cell lung cancer (NSCLC) patients who are adequate for targeted treatment, a total of 137 NSCLC cases were analyzed by fluorescence in situ hybridization (FISH) for anaplastic lymphoma kinase (ALK) rearrangements, and Epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were evaluated by quantitative real-time PCR (qRT-PCR) platform combining amplification refractory mutation system (ARMS) primers and TaqMan probes. Cytological specimens included 91 fine-needle aspirates, 5 fibreoptic bronchoscopic derived samples and 41 pleural effusions. Among 137 NSCLCs analyzed for ALK FISH, 16 (11.7%, of 137) were detected to harbor ALK rearrangement. FISH positive cases were all defined as adenocarcinoma (ADC) histologic subtype and the FNA samples showed the highest ALK positive rate (13.2%, 12/91). Of the 9 ALK FISH positive patients who received crizotinib treatment, 8 (88.9%) patients exhibited tumor regression. In addition, 60 (44.8%, of 134) cases were found to harbor EGFR mutations and 22 patients with EGFR sensitive mutations who received gefitinib or erlotinib treatment showed a median PFS of 16.0 months. Mutations of KRAS occurred in 8 (6.0%, of 134) cases and this was mutually exclusive from EGFR mutation. Our results demonstrated that ALK FISH and EGFR, KRAS mutational analysis on cytological specimens are sensitive methods for screening advanced stage NSCLC patients who are adequate for targeted treatment.
Highlights
Non-small-cell lung cancer (NSCLC), which accounts for approximately 85% of lung cancers, has been largely identified by oncogenic driver mutations with potential opportunities for targeted therapies [1, 2]
We investigate the use of anaplastic lymphoma kinase (ALK) fluorescence in situ hybridization (FISH) and epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene homolog (KRAS) mutational testing on cytological specimens and to evaluate progression-free survival (PFS) of the patients who received targeted therapies
The diagnosis of advanced-stage NSCLC is usually based on a small amount of cytological specimens, the use of ALK FISH and EGFR, KRAS mutational testing on cytological specimens is gradually becoming a necessity in the routine molecular pathological diagnosis
Summary
Non-small-cell lung cancer (NSCLC), which accounts for approximately 85% of lung cancers, has been largely identified by oncogenic driver mutations with potential opportunities for targeted therapies [1, 2]. Clinical studies have shown that locally advanced or metastatic NSCLC patients harboring ALK gene rearrangement are highly sensitive to Crizotinib, which is a small molecular inhibitor of ALK tyrosine kinase [8, 9]. 60% of patients with NSCLC are diagnosed at a late stage for the first time [11]. These patients are not suitable for the resection of the primary tumor, and the only pathologic material guiding systemic therapy should be small biopsy or cytological specimens. We investigate the use of ALK FISH and EGFR, KRAS mutational testing on cytological specimens and to evaluate PFS of the patients who received targeted therapies
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