PMID- 30572846 OWN - NLM STAT- MEDLINE DCOM- 20190327 LR - 20200225 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 18 IP - 1 DP - 2018 Dec 20 TI - Application of Ventana immunocytochemical analysis on ThinPrep cytology slides for detection of ALK rearrangement in patients with advanced non-small-cell lung cancer. PG - 1277 LID - 10.1186/s12885-018-5184-x [doi] LID - 1277 AB - BACKGROUND: Ventana ALK (D5F3) screening of anaplastic lymphoma kinase (ALK) gene rearrangement in tissue specimens has been approved by US FDA (Food and Drug Administration) to select treatment for non-small-cell lung carcinoma (NSCLC). However, tumor tissues are often not readily obtainable, and cytology specimens and may be the only tumor material available for diagnosis and molecular marker analysis. In this study, we evaluated the feasibility of ALK immunocytochemistry (ICC) on ThinPrep slides and determined a suitable scoring system for interpretation of the results. METHODS: One hundred twenty-one fine-needle aspirate (FNA) specimens from metastatic lesions of NSCLC were analyzed. ALK rearrangement was detected on ThinPrep cytology slides using the Ventana immunocytochemistry ALK-D5F3 system, which adopts two scoring systems for interpretation of the ICC results. The results were subsequently confirmed by reverse transcription polymerase chain reaction (RT-PCR) analysis and fluorescence in situ hybridization (FISH). RESULTS: Among the 121 ICC specimens, 16 that were considered ALK-positive by either scoring system were referred for PCR analysis. Among the ALK ICC-negative cases, 33 had correlated FISH ALK results. A total of 49 specimens that exhibited either a positive or negative ICC result with a correlated ALK status were analyzed statistically. ICC results showed a high concordance rate with the results of PCR/FISH analysis. The sensitivity and specificity of ALK ICC by the binary scoring algorithm were 68.75 and 96.97%, respectively. These values increased to 93.75 and 96.97%, respectively, when interpreted by the semiquantified interpretation system. CONCLUSIONS: ALK ICC analysis on ThinPrep slides is a reliable ALK testing method, and the semiquantified interpretation system on cytology specimens is recommended rather than the binary scoring algorithm on tissue specimens. FAU - Guo, Hui Qin AU - Guo HQ AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Jia, Jia AU - Jia J AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Zhao, Lin Lin AU - Zhao LL AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Zhao, Huan AU - Zhao H AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Wang, Cong AU - Wang C AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Sun, Yue AU - Sun Y AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Ying, Jian Ming AU - Ying JM AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Guo, Lei AU - Guo L AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Cao, Jian AU - Cao J AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. FAU - Zhang, Zhi Hui AU - Zhang ZH AD - Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Panjiayuan 17 in the South, Beijing, 100021, China. zhangzhh9@163.com. LA - eng GR - 81641115/National Natural Science Foundation of China/ GR - 2017-I2M-1-006/CAMS Innovation Fund for Medical Sciences/ PT - Journal Article DEP - 20181220 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) SB - IM MH - Adenocarcinoma MH - Aged MH - Anaplastic Lymphoma Kinase/*genetics/isolation & purification MH - Biopsy, Fine-Needle MH - Carcinoma, Non-Small-Cell Lung/*genetics/pathology MH - *Cytodiagnosis MH - Female MH - Gene Rearrangement/genetics MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasm Staging PMC - PMC6302402 OTO - NOTNLM OT - ALK rearrangement OT - Binary scoring algorithm OT - Non-small-cell lung cancer OT - Semiquantified interpretation system OT - ThinPrep slides COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study protocol was reviewed and approved by the Ethics Committee of the National Cancer Center/Cancer Hospital. All the patients were required to sign an informed consent form explaining the risks of FNA before the FNA examination. At this time, they also gave their informed consent to the present study by signing the paper's informed consent form. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/12/24 06:00 MHDA- 2019/03/28 06:00 PMCR- 2018/12/20 CRDT- 2018/12/22 06:00 PHST- 2017/12/04 00:00 [received] PHST- 2018/12/04 00:00 [accepted] PHST- 2018/12/22 06:00 [entrez] PHST- 2018/12/24 06:00 [pubmed] PHST- 2019/03/28 06:00 [medline] PHST- 2018/12/20 00:00 [pmc-release] AID - 10.1186/s12885-018-5184-x [pii] AID - 5184 [pii] AID - 10.1186/s12885-018-5184-x [doi] PST - epublish SO - BMC Cancer. 2018 Dec 20;18(1):1277. doi: 10.1186/s12885-018-5184-x.