Detection of ALK Gene Rearrangements in Pulmonary Adenocarcinoma: Assess for Typical and Atypical Abnormal Patterns
Kaaren K Reichard. University of New Mexico, Albuquerque, NM
Background: A subset of pulmonary adenocarcinomas harbors an ALK gene rearrangement. The genetic alteration corresponds to an intrachromosomal rearrangement on 2p resulting in an EML4-ALK fusion at the molecular level. Detection of an ALK rearrangement is critical for treatment as an ALK targeted therapy, crizotinib, is available. When attempting to detect this rearrangement by fluorescence in situ hybridization (FISH) using an ALK break-apart probe, laboratorians must be cognizant of the typical abnormal but also potential atypical, yet still abnormal, patterns.
Design: We identified 9 cases of ALK-rearranged pulmonary adenocarcinomas detected by FISH from our files from 2010 to August 2011. FISH using an ALK break-apart probe was performed on paraffin-embedded, formalin-fixed whole tissue sections in all cases. Analysis was performed using an automated image analysis system, MetaSystems™, and verified by manual inspection. Positivity for an ALK rearrangement is defined in our laboratory as separation of the orange and green signals by at least four probe signal widths in >20% of tumor nuclei.
Results: The clinical, pathologic and genetic characteristics of our nine cases are shown in Table 1. Five of the nine cases showed “atypical”, yet still abnormal, FISH patterns corresponding to an ALK rearrangement. These patterns include loss of the green, 5', centromeric probe (1F1O, 2F1O) or the presence of multiple copies of the rearrangement in each cell (1F2O2G).
Conclusions: Reliable detection of an ALK gene rearrangement in pulmonary adenocarcinoma requires knowledge of the typical expected abnormal pattern and atypical variants which correspond to the EML4-ALK molecular fusion. Although we evaluated only a small cohort of cases (9), we found that the majority of our cases showed an atypical scoring pattern. This is significant for ensuring the correct reporting of a result given an available targeted therapeutic agent.
Monday, March 19, 2012 1:00 PM
Poster Session II # 288, Monday Afternoon