Frequency of ALK Translocations in 2560 Non-Small Cell Lung Cancer Samples
John Glassco, Tommy Ha, Derek Bouman, Paul Choppa, Kenneth J Bloom. Clarient, A GE Healthcare Company, Aliso Viejo, CA
Background: The anaplastic lymphoma kinase (ALK) gene codes for a transmembrane receptor tyrosine kinase (RTK) in the insulin receptor superfamily. It has been identified as the fusion partner in a number of different malignancies and has long been suspected as a driver oncogene in these conditions. Although a number of studies have been conducted, the frequency of EML4-ALK in NSCLC ranges from 2-7% likely due to variability of patient selection and testing platforms. Crizotinib was recently approved for the treatment of ALK positive NSCLC patients as determined by the presence of an ALK gene rearrangement based on a companion diagnostic FISH assay. We assessed a large series of patients to determine the positivity rate of this assay in a US based population.
Design: 2560 consecutive formalin fixed paraffin embedded non-small cell lung cancer samples sent to our laboratory for determination of ALK rearrangement status were assessed using the Abbott LSI ALK break apart rearrangement FISH probe. Fifty tumor cells were enumerated for the presence of a break apart signal which was considered as present when at least one set of orange and green signals were 2 or more signal diameters apart or when a single orange signal without a corresponding green signal was observed in more than 15% of the tumor cells.
Results: Of the 2560 samples tested, 163 did not contain sufficient tumor content to conduct testing and 39 (1.5%) samples demonstrated suboptimal hybridization. 79 (3.35%) samples demonstrated an ALK rearrangement and 2279 had no detectable alteration.
Conclusions: The Abbott LSI ALK break apart FISH probe has excellent performance characteristics with a failure/suboptimal hybridization rate of approximately 1.5% in our hands. Although the ALK break apart probe does not specifically identify EML4 as the ALK fusion partner, the frequency of ALK rearrangements was 3.35% in our series of NSCLC patients. This number agrees with the expected rates based on previous studies and helps define the positivity rate in a US based population.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 304, Tuesday Morning