PMID- 26789109 OWN - NLM STAT- MEDLINE DCOM- 20161220 LR - 20181202 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 7 DP - 2016 Feb 16 TI - Assessment of cytology based molecular analysis to guide targeted therapy in advanced non-small-cell lung cancer. PG - 8332-40 LID - 10.18632/oncotarget.6671 [doi] AB - 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. FAU - Li, Wenbin AU - Li W AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Zhang, Zhihui AU - Zhang Z AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Guo, Lei AU - Guo L AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Qiu, Tian AU - Qiu T AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Ling, Yun AU - Ling Y AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Cao, Jian AU - Cao J AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Guo, Huiqin AU - Guo H AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Zhao, Huan AU - Zhao H AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Li, Lin AU - Li L AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. FAU - Ying, Jianming AU - Ying J AD - Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Antineoplastic Agents) RN - 0 (KRAS protein, human) RN - 0 (RNA, Messenger) RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Alk protein, rat) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) SB - IM MH - Adenocarcinoma/drug therapy/genetics/pathology MH - Adult MH - Aged MH - Aged, 80 and over MH - Anaplastic Lymphoma Kinase MH - Antineoplastic Agents/therapeutic use MH - Biopsy, Fine-Needle MH - Carcinoma, Adenosquamous/drug therapy/genetics/pathology MH - Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/*pathology MH - Carcinoma, Squamous Cell/drug therapy/genetics/pathology MH - Cytodiagnosis/*methods MH - ErbB Receptors/*genetics MH - Female MH - Follow-Up Studies MH - Gene Rearrangement MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Lung Neoplasms/drug therapy/genetics/pathology MH - Male MH - Middle Aged MH - *Molecular Targeted Therapy MH - Mutation/*genetics MH - Neoplasm Staging MH - Prognosis MH - Proto-Oncogene Proteins p21(ras)/*genetics MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Receptor Protein-Tyrosine Kinases/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survival Rate PMC - PMC4884996 OTO - NOTNLM OT - ALK OT - EGFR OT - fluorescence in situ hybridization OT - patient outcomes OT - targeted therapy COIS- CONFLICTS OF INTEREST The authors declare no competing financial interests. EDAT- 2016/01/21 06:00 MHDA- 2016/12/21 06:00 PMCR- 2016/02/16 CRDT- 2016/01/21 06:00 PHST- 2015/08/05 00:00 [received] PHST- 2015/11/25 00:00 [accepted] PHST- 2016/01/21 06:00 [entrez] PHST- 2016/01/21 06:00 [pubmed] PHST- 2016/12/21 06:00 [medline] PHST- 2016/02/16 00:00 [pmc-release] AID - 6671 [pii] AID - 10.18632/oncotarget.6671 [doi] PST - ppublish SO - Oncotarget. 2016 Feb 16;7(7):8332-40. doi: 10.18632/oncotarget.6671.