Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma

IHC score algorithm for FISH

Eunhee S. Yi, Jennifer M. Boland, Joseph Maleszewski, Anja Roden, Andre M. Oliveira, Marie Christine Aubry, Michele R. Erickson-Johnson, Bolette L. Caron, Yan Li, Hui Tang, Shawn Stoddard, Jason Wampfler, Kimary Kulig, Ping Yang

Research output: Contribution to journalArticle

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Abstract

Introduction: Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach. Methods: One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue. Results: Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≤10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH-. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative. Conclusions: IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.

Original languageEnglish (US)
Pages (from-to)459-465
Number of pages7
JournalJournal of Thoracic Oncology
Volume6
Issue number3
DOIs
StatePublished - Mar 2011

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Gene Rearrangement
Fluorescence In Situ Hybridization
Non-Small Cell Lung Carcinoma
Immunohistochemistry
Staining and Labeling
Molecular Probes
Epidermal Growth Factor
Gold
Paraffin
Formaldehyde
Lung Neoplasms
Adenocarcinoma
Color
Monoclonal Antibodies
Breast Neoplasms
Costs and Cost Analysis
Sensitivity and Specificity

Keywords

  • Adenocarcinoma
  • Anaplastic lymphoma kinase
  • Fluorescent in situ hybridization
  • Immunohistochemistry
  • Non-small cell lung carcinoma

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma : IHC score algorithm for FISH. / Yi, Eunhee S.; Boland, Jennifer M.; Maleszewski, Joseph; Roden, Anja; Oliveira, Andre M.; Aubry, Marie Christine; Erickson-Johnson, Michele R.; Caron, Bolette L.; Li, Yan; Tang, Hui; Stoddard, Shawn; Wampfler, Jason; Kulig, Kimary; Yang, Ping.

In: Journal of Thoracic Oncology, Vol. 6, No. 3, 03.2011, p. 459-465.

Research output: Contribution to journalArticle

Yi, ES, Boland, JM, Maleszewski, J, Roden, A, Oliveira, AM, Aubry, MC, Erickson-Johnson, MR, Caron, BL, Li, Y, Tang, H, Stoddard, S, Wampfler, J, Kulig, K & Yang, P 2011, 'Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH', Journal of Thoracic Oncology, vol. 6, no. 3, pp. 459-465. https://doi.org/10.1097/JTO.0b013e318209edb9
Yi, Eunhee S. ; Boland, Jennifer M. ; Maleszewski, Joseph ; Roden, Anja ; Oliveira, Andre M. ; Aubry, Marie Christine ; Erickson-Johnson, Michele R. ; Caron, Bolette L. ; Li, Yan ; Tang, Hui ; Stoddard, Shawn ; Wampfler, Jason ; Kulig, Kimary ; Yang, Ping. / Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma : IHC score algorithm for FISH. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 3. pp. 459-465.
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abstract = "Introduction: Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach. Methods: One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue. Results: Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≤10{\%} of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH-. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8{\%}, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative. Conclusions: IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.",
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T1 - Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma

T2 - IHC score algorithm for FISH

AU - Yi, Eunhee S.

AU - Boland, Jennifer M.

AU - Maleszewski, Joseph

AU - Roden, Anja

AU - Oliveira, Andre M.

AU - Aubry, Marie Christine

AU - Erickson-Johnson, Michele R.

AU - Caron, Bolette L.

AU - Li, Yan

AU - Tang, Hui

AU - Stoddard, Shawn

AU - Wampfler, Jason

AU - Kulig, Kimary

AU - Yang, Ping

PY - 2011/3

Y1 - 2011/3

N2 - Introduction: Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach. Methods: One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue. Results: Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≤10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH-. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative. Conclusions: IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.

AB - Introduction: Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach. Methods: One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue. Results: Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≤10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH-. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative. Conclusions: IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.

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KW - Anaplastic lymphoma kinase

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KW - Immunohistochemistry

KW - Non-small cell lung carcinoma

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