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.
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.
Authors: Diana Taheri; David J Zahavi; Maria Del Carmen Rodriguez; Abdelrazak Meliti; Neda Rezaee; Raluca Yonescu; Bernardo F P Ricardo; Shahaboddin Dolatkhah; Yi Ning; Justin A Bishop; George J Netto; Rajni Sharma Journal: Virchows Arch Date: 2016-06-06 Impact factor: 4.064
Authors: Bríd M Ryan; Yi Wang; Jin Jen; Eunhee S Yi; Susan Olivo-Marston; Ping Yang; Curtis C Harris Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-04-22 Impact factor: 4.254
Authors: Christian Rolfo; Francesco Passiglia; Marta Castiglia; Luis E Raez; Paul Germonpre; Ignacio Gil-Bazo; Karen Zwaenepoel; Annemieke De Wilde; Giuseppe Bronte; Antonio Russo; Jan P Van Meerbeeck; Paul Van Schil; Patrick Pauwels Journal: Transl Lung Cancer Res Date: 2014-08
Authors: Teresa Morán; Vanesa Quiroga; María de Los Llanos Gil; Laia Vilà; Nuria Pardo; Enric Carcereny; Laia Capdevila; Ana M Muñoz-Mármol; Rafael Rosell Journal: Transl Lung Cancer Res Date: 2013-04
Authors: Marina Pekar-Zlotin; Fred R Hirsch; Lior Soussan-Gutman; Maya Ilouze; Addie Dvir; Theresa Boyle; Murry Wynes; Vincent A Miller; Doron Lipson; Gary A Palmer; Siraj M Ali; Shlomi Dekel; Ronen Brenner; Paul A Bunn; Nir Peled Journal: Oncologist Date: 2015-02-26