ALK Testing in Lung Adenocarcinoma. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Martin, Vittoria; Bernasconi, Barbara; Merlo, Elisabetta; Balzarini, Piera; Vermi, William; Riva, Alice; Chiaravalli, Anna Maria; Frattini, Milo; Sahnane, Nora; Facchetti, Fabio; Mazzucchelli, Luca; Sessa, Fausto; Tibiletti, Maria Grazia
• Is Part Of: Journal of thoracic oncology. Volume 10:Issue 4(2015)
• Publication Date: 2015-04
• Subjects: Chest -- Cancer -- Periodicals; Thoracic Neoplasms -- Periodicals; 616.99494005
• DOI: 10.1097/JTO.0000000000000444
• Languages: English
• ISSNs: 1556-0864

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Introduction:</title> <p>Anaplastic lymphoma kinase (<italic>ALK</italic>) gene rearrangement characterizes a subgroup of patients with lung adenocarcinoma who may benefit from ALK inhibitors. Fluorescence in situ hybridization (FISH) with a break-apart/split-signal strategy is the gold standard to investigate <italic>ALK</italic>. The cutoff to define <italic>ALK</italic> positivity has been settled at 15% or greater. A subset of patients has <italic>ALK</italic> borderline status, showing 15% ± 5% positive cells. Several aspects, both biological and technical, might influence signals evaluation, making FISH interpretation a challenging task. To improve <italic>ALK</italic> evaluation, we classified the different FISH patterns on the basis of the type of the split signals, namely short, long, far away, and deleted.</p> </sec> <sec> <title>Methods:</title> <p>We investigated <italic>ALK</italic> gene status by FISH in 244 lung adenocarcinomas and in a series of <italic>ALK</italic> negative cell lines samples, collected in three Institutions.</p> </sec> <sec> <title>Results:</title> <p> <italic>ALK</italic> positive profile was found in 12% of patients; long, deleted, and far-away splits were the primary patterns observed. <italic>ALK</italic> borderline profile characterized 10% of samples; long and deleted splits were significantly more frequent in those borderline finally classified as <italic>ALK</italic> positive, whereas short split were mostly detected in those borderline patients finally classified as <italic>ALK</italic> negative (<italic>p</italic> = 3.4 × 10<sup>−3</sup>). In the <italic>ALK</italic> negative control series, short split was the predominant pattern. Concordance was observed among different operators and probes for both samples and controls.</p> </sec> <sec> <title>Conclusions:</title> <p>Difficulties in <italic>ALK</italic> FISH signal interpretation might be bypassed using this detailed scoring system, which is highly reproducible, helps clarify borderline samples (according to split type), and provides experimental evidence that 15% is a reasonable cutoff to overcome the assay-dependent background noise.</p> </sec> </abstract>