Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC.

Introduction: rearrangements occur in 1% to 2% NSCLCs. Since no clinically validated RET antibody is currently available, fluorescence in situ hybridization (FISH) is often used as a screening tool to identify patients likely to benefit from RET-targeted therapy. In this study, we performed a comprehensive review of publications in which -rearrangement testing was performed by FISH and compared the methods and results with our data.

Methods: The findings of an electronic search for publications using -FISH in lung cancer were compared with the results obtained at the Grenoble University Hospital where 784 , , -, and -negative NSCLCs were tested by break-apart FISH and confirmed by RNA-sequencing (RNA-seq).

Results: Out of the 85 publications using -FISH analysis, 52 pertained to patients with lung cancer. The most often used positivity threshold was 15%. Six publications compared -FISH with at least one other molecular technique on at least eight samples, and the concordance was variable, from 5.9% to 66.7% for FISH-positive cases. Regarding our data, out of the 784 analyzed samples, 32 (4%) were positive by -FISH. The concordance between -FISH and RNA-seq in -FISH positive samples was 69%.

Conclusions: Overall, both existing literature and our data suggest that -FISH testing can be used for rapid screening of rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm -FISH-positive cases is essential for ensuring that only patients likely to benefit from -target therapy receive the treatment.