Assessment of cytology based molecular analysis to guide targeted therapy in advanced non-small-cell lung cancer.
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.
['Li|Wenbin|W|', 'Zhang|Zhihui|Z|', 'Guo|Lei|L|', 'Qiu|Tian|T|', 'Ling|Yun|Y|', 'Cao|Jian|J|', 'Guo|Huiqin|H|', 'Zhao|Huan|H|', 'Li|Lin|L|', 'Ying|Jianming|J|']
D000230:Adenocarcinoma D000328:Adult D000368:Aged D000369:Aged, 80 and over D000077548:Anaplastic Lymphoma Kinase D000970:Antineoplastic Agents D044963:Biopsy, Fine-Needle D018196:Carcinoma, Adenosquamous D002289:Carcinoma, Non-Small-Cell Lung D002294:Carcinoma, Squamous Cell D003581:Cytodiagnosis D066246:ErbB Receptors D005260:Female D005500:Follow-Up Studies D015321:Gene Rearrangement D059014:High-Throughput Nucleotide Sequencing D006801:Humans D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D058990:Molecular Targeted Therapy D009154:Mutation D009367:Neoplasm Staging D011379:Prognosis D016283:Proto-Oncogene Proteins p21(ras) D012333:RNA, Messenger D060888:Real-Time Polymerase Chain Reaction D020794:Receptor Protein-Tyrosine Kinases D020133:Reverse Transcriptase Polymerase Chain Reaction D015996:Survival Rate
targeted therapy fluorescence in situ hybridization ALK EGFR patient outcomes