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

Research output: Contribution to journalArticle

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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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Carcinoma in Situ
Fluorescence In Situ Hybridization
Non-Small Cell Lung Carcinoma
Cell Biology
Paraffin
Gene Rearrangement
Immunohistochemistry
anaplastic lymphoma kinase
United States Food and Drug Administration
Fine Needle Biopsy
Color
Sensitivity and Specificity

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Minca, Eugen C. ; Lanigan, Christopher P. ; Reynolds, Jordan P. ; Wang, Zhen ; Ma, Patrick Chi-Chung ; Cicenia, Joseph ; Almeida, Francisco A. ; Pennell, Nathan A. ; Tubbs, Raymond R. / ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material. In: Journal of Thoracic Oncology. 2014 ; Vol. 9, No. 4. pp. 464-468.
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title = "ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material",
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.",
author = "Minca, {Eugen C.} and Lanigan, {Christopher P.} and Reynolds, {Jordan P.} and Zhen Wang and Ma, {Patrick Chi-Chung} and Joseph Cicenia and Almeida, {Francisco A.} and Pennell, {Nathan A.} and Tubbs, {Raymond R.}",
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Minca, EC, Lanigan, CP, Reynolds, JP, Wang, Z, Ma, PC-C, Cicenia, J, Almeida, FA, Pennell, NA & Tubbs, RR 2014, 'ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material', Journal of Thoracic Oncology, vol. 9, no. 4, pp. 464-468. https://doi.org/10.1097/JTO.0000000000000104

ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material. / Minca, Eugen C.; Lanigan, Christopher P.; Reynolds, Jordan P.; Wang, Zhen; Ma, Patrick Chi-Chung; Cicenia, Joseph; Almeida, Francisco A.; Pennell, Nathan A.; Tubbs, Raymond R.

In: Journal of Thoracic Oncology, Vol. 9, No. 4, 01.04.2014, p. 464-468.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ALK status testing in non-small-cell lung carcinoma by FISH on ThinPrep slides with cytology material

AU - Minca, Eugen C.

AU - Lanigan, Christopher P.

AU - Reynolds, Jordan P.

AU - Wang, Zhen

AU - Ma, Patrick Chi-Chung

AU - Cicenia, Joseph

AU - Almeida, Francisco A.

AU - Pennell, Nathan A.

AU - Tubbs, Raymond R.

PY - 2014/4/1

Y1 - 2014/4/1

N2 - 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.

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.

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