TY - JOUR
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 J.
AU - Roden, Anja C.
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
N1 - Funding Information:
Supported by an Outcomes Research service agreement with Pfizer Inc. Editorial support was provided by Jessica Stevens at ACUMED (Tytherington, UK).
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.
KW - Adenocarcinoma
KW - Anaplastic lymphoma kinase
KW - Fluorescent in situ hybridization
KW - Immunohistochemistry
KW - Non-small cell lung carcinoma
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U2 - 10.1097/JTO.0b013e318209edb9
DO - 10.1097/JTO.0b013e318209edb9
M3 - Article
C2 - 21278610
AN - SCOPUS:79951774364
SN - 1556-0864
VL - 6
SP - 459
EP - 465
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 3
ER -