title: Assessment of cytology based molecular analysis to guide targeted therapy in advanced non-small-cell lung cancer.
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.
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ying
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044963:Biopsy, Fine-Needle; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D003581:Cytodiagnosis / Q000379:methods*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D012333:RNA, Messenger; C000626173:ALK protein, human; C000626175:Alk protein, rat; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: ALK; EGFR; fluorescence in situ hybridization; patient outcomes; targeted therapy