ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material

Eugen C. Minca, Christopher P. Lanigan, Jordan P. Reynolds, Zhen Wang, Patrick Chi-Chung Ma, Joseph Cicenia, Francisco A. Almeida, Nathan A. Pennell, Raymond R. Tubbs

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)464-468
Number of pages5
JournalJournal of Thoracic Oncology
Volume9
Issue number4
DOIs
StatePublished - Apr 1 2014

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Minca, E. C., Lanigan, C. P., Reynolds, J. P., Wang, Z., Ma, P. C-C., Cicenia, J., Almeida, F. A., Pennell, N. A., & Tubbs, R. R. (2014). ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material. Journal of Thoracic Oncology, 9(4), 464-468. https://doi.org/10.1097/JTO.0000000000000104