PMID- 24736067 OWN - NLM STAT- MEDLINE DCOM- 20150120 LR - 20181202 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 4 DP - 2014 Apr TI - ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material. PG - 464-8 LID - 10.1097/JTO.0000000000000104 [doi] AB - INTRODUCTION: Oncogenic anaplastic lymphoma kinase (ALK) gene rearrangements in non-small-cell lung carcinomas (NSCLC) provide the basis for targeted therapy with crizotinib and other specific ALK inhibitors. Treatment eligibility is conventionally determined by the Food and Drug Administration-approved companion diagnostic fluorescence in situ hybridization (FISH) assay on paraffin-embedded tissue (PET). On limited samples such as fine needle aspiration-derived cytoblocks, FISH for ALK is often uninformative. FISH performed on liquid-based ThinPrep slides (ThinPrep-FISH) may represent a robust alternative. METHODS: Two hundred thirty cytology samples from 217 patients with advanced NSCLC, including a consecutive series of 179 specimens, were used to generate matched ThinPrep slides and paraffin cytoblocks. The same ThinPrep slides used for cytologic diagnosis were assessed by standard ALK break-apart two-color probe FISH, after etching of tumor areas. Ultrasensitive ALK immunohistochemistry (IHC) on corresponding cytoblocks [D5F3 antibody, OptiView signal amplification] served as the reference data set. RESULTS: ThinPrep-FISH ALK signals were robust in 228 of 230 cases and not compromised by nuclear truncation inherent in paraffin-embedded tissue-FISH; only two samples displayed no signals. Nine of 178 informative cases (5%) in the consecutive series and 18 of 228 informative cases (7.8%) overall were ALK rearranged by ThinPrep-FISH. In 154 informative matched ThinPrep-FISH and cytoblock-IHC samples, 152 were concordant (10, 6.5% ALK status positive; 142, 92.2% ALK status negative), and two (1.3%) were ThinPrep-FISH positive but IHC negative (sensitivity 100%, specificity 98.6%, overall agreement 98.7%). CONCLUSION: Detection of ALK gene rearrangements in liquid cytology ThinPrep slides derived from patients with NSCLC can be confidently used for clinical ALK molecular testing. FAU - Minca, Eugen C AU - Minca EC AD - *Departments of Molecular Pathology, Cytopathology, and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland, Ohio; daggerDepartments of Translational Hematology and Oncology Research, and Solid Tumor Oncology, Taussig Cancer Institute, Cleveland, Ohio; and double daggerRespiratory Institute, Cleveland Clinic Foundation, Cleveland, Ohio. FAU - Lanigan, Christopher P AU - Lanigan CP FAU - Reynolds, Jordan P AU - Reynolds JP FAU - Wang, Zhen AU - Wang Z FAU - Ma, Patrick C AU - Ma PC FAU - Cicenia, Joseph AU - Cicenia J FAU - Almeida, Francisco A AU - Almeida FA FAU - Pennell, Nathan A AU - Pennell NA FAU - Tubbs, Raymond R AU - Tubbs RR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Adenocarcinoma/*diagnosis/genetics/metabolism MH - Anaplastic Lymphoma Kinase MH - Carcinoma, Non-Small-Cell Lung/*diagnosis/genetics/metabolism MH - Cytodiagnosis/*methods MH - *Gene Rearrangement MH - Humans MH - Immunoenzyme Techniques MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*diagnosis/genetics/metabolism MH - Neoplasm Staging MH - Prognosis MH - Receptor Protein-Tyrosine Kinases/*genetics/*metabolism EDAT- 2014/04/17 06:00 MHDA- 2015/01/21 06:00 CRDT- 2014/04/17 06:00 PHST- 2014/04/17 06:00 [entrez] PHST- 2014/04/17 06:00 [pubmed] PHST- 2015/01/21 06:00 [medline] AID - S1556-0864(15)30241-0 [pii] AID - 10.1097/JTO.0000000000000104 [doi] PST - ppublish SO - J Thorac Oncol. 2014 Apr;9(4):464-8. doi: 10.1097/JTO.0000000000000104.