Fluorescence in situ hybridization analysis of the ALK gene in 2,045 non-small cell lung cancer patients from North-Western Spain (Galicia)

Abstract

Identification of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is a standard diagnostic test in patients with advanced non-small cell lung cancer (NSCLC). The current study describes the experience of ALK rearrangement detection of a referral center in the public health care system of Galicia in North-Western Spain. The fluorescence in situ hybridization (FISH) patterns of the ALK gene and the clinical and pathological features of these patients are reported. This study is also of interest for comparative purposes due to the relative geographical isolation of the area, which could have contributed to particular genetic features. A total of 2,045 tissue samples from NSCLC patients were collected between October 2010 and July 2015 and tested for ALK rearrangements by FISH. Examination of 1,686 paraffin-embedded tissue specimens and 395 cytological samples (306 cell block preparations and 53 cytological smears) was conducted, and any associations between the FISH results and clinicopathological features were assessed. The rate of successful evaluation was marginally higher in tissue samples than in cytological samples (92.9% vs. 84.1%); this difference was not significant. ALK rearrangements were identified in 82 patients(4%): 65 (79.3%) in tissue specimens, 15 (18.3%) in cell block samples and 2 (2.4%) in cytological smears. This genetic translocation appeared to be associated with a non-smoking history, younger age, female gender, stage IV and adenocarcinoma histological type. The findings demonstrate that ALK evaluation by FISH is feasible in tissue and cytological samples. The clinical and pathological features of the ALK-positive series of patients are similar to those previously reported in the literature.

Detection of alk gene rearrangements in non-small cell lung cancer by immunocytochemistry and fluorescence in situ hybridization on cytologic samples

“…ALK gene rearrangements are seen in 1.9-6.8% cases of NSCLCs (6). The most common ALK gene rearrangement effusion was found to be higher in patients with ALK gene rearrangement as seen in the previous studies; however, this was not statistically significant (18,19).…”

“…Anaplastic lymphoma kinase (ALK), is a tyrosine kinase receptor, encoded by the ALK gene. ALK gene rearrangements are seen in 1.9-6.8% cases of NSCLCs (6). The most common genetic rearrangement involves the echinoderm microtubule associated protein-like 4 (EML4) and ALK leading to formation of the EML4-ALK fusion gene that encodes for a chimeric protein with intrinsic tyrosine kinase activity.…”

ALK and ROS1 testing on lung cancer cytologic samples: Perspectives

“…Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA), as an alternative to mediastinoscopy, is a minimally invasive procedure that integrates real‐time evaluation during bronchoscopy and sampling of mediastinal and pulmonary hilar lymph nodes and parenchymal masses in patients with advanced NSCLC for morphologic diagnosis, staging, and molecular analysis . Several studies, which are summarized in Table , have demonstrated that cell blocks obtained by EBUS‐TBNA can be reliably used for ALK FISH testing; indeed, informative results were obtained in greater than 90% of cases, and the rearrangement detection rate was similar (3.9%) to that of surgical specimens (3.4%) …”

“…In the 1 discordant case, an ALK rearrangement was detected on the direct smear, and RT-PCR confirmed the rearrangement. 32 Accordingly, FISH performed using cytologic smears provides information about ALK status in most cases, 33,34 and FISH positivity on cytology reliably predicts tumor response. 35 Indeed, of the 9 ALK FISH-positive patients who received crizotinib treatment, 8 (88.9%) exhibited tumor regression.…”

Identification of ALK-positive patients with advanced NSCLC and real-world clinical experience with crizotinib in Spain (IDEALK study)

“…In the last two decades the treatment of NSCLC has been revolutionized by the emergence of molecular-driven targeted therapies such as small molecule tyrosine kinase inhibitors and immunotherapy, which has led to greatly increased survival and quality of life in selected patients. Since its identification in 2007 [4], translocations of the anaplastic lymphoma kinase (ALK) gene, which lead to activation of the ALK tyrosine kinase domain and oncogenesis, have been identified in approximately 3-6 % of all NSCLC cases [5][6][7][8][9]. Patients with NSCLC driven by ALK rearrangements may benefit from ALK tyrosine kinase inhibitor (TKI) therapies [10].…”