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J Thorac Oncol. 2014 Apr;9(4):464-8. doi: 10.1097/JTO.0000000000000104.

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

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1
*Departments of Molecular Pathology, Cytopathology, and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland, Ohio; †Departments of Translational Hematology and Oncology Research, and Solid Tumor Oncology, Taussig Cancer Institute, Cleveland, Ohio; and ‡Respiratory Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

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.

PMID:
24736067
DOI:
10.1097/JTO.0000000000000104
[Indexed for MEDLINE]
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