Research Papers:

Assessment of cytology based molecular analysis to guide targeted therapy in advanced non-small-cell lung cancer

Wenbin Li, Zhihui Zhang, Lei Guo, Tian Qiu, Yun Ling, Jian Cao, Huiqin Guo, Huan Zhao, Lin Li and Jianming Ying _

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Oncotarget. 2016; 7:8332-8340. https://doi.org/10.18632/oncotarget.6671

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Wenbin Li1,*, Zhihui Zhang1,*, Lei Guo1, Tian Qiu1, Yun Ling1, Jian Cao1, Huiqin Guo1, Huan Zhao1, Lin Li1, Jianming Ying1

1Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China

*These authors have contributed equally to this work

Correspondence to:

Jianming Ying, e-mail: [email protected]

Keywords: ALK, fluorescence in situ hybridization, EGFR, targeted therapy, patient outcomes

Received: August 05, 2015     Accepted: November 25, 2015     Published: December 18, 2015


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.

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