title: Screening for ALK abnormalities in central nervous system metastases of non-small-cell lung cancer.
abstract: Anaplastic lymphoma kinase (ALK) gene rearrangement was reported in 3%-7% of primary non-small-cell lung cancer (NSCLC) and its presence is commonly associated with adenocarcinoma (AD) type and non-smoking history. ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed efficiency in patients with primary NSCLC harboring ALK gene rearrangement. Moreover, response to ALK TKIs was observed in central nervous system (CNS) metastatic lesions of NSCLC. However, there are no reports concerning the frequency of ALK rearrangement in CNS metastases. We assessed the frequency of ALK abnormalities in 145 formalin fixed paraffin embedded (FFPE) tissue samples from CNS metastases of NSCLC using immunohistochemical (IHC) automated staining (BenchMark GX, Ventana, USA) and fluorescence in situ hybridization (FISH) technique (Abbot Molecular, USA). The studied group was heterogeneous in terms of histopathology and smoking status. ALK abnormalities were detected in 4.8% (7/145) of CNS metastases. ALK abnormalities were observed in six AD (7.5%; 6/80) and in single patients with adenosuqamous lung carcinoma. Analysis of clinical and demographic factors indicated that expression of abnormal ALK was significantly more frequently observed (P = 0.0002; χ2= 16.783) in former-smokers. Comparison of IHC and FISH results showed some discrepancies, which were caused by unspecific staining of macrophages and glial/nerve cells, which constitute the background of CNS tissues. Their results indicate high frequency of ALK gene rearrangement in CNS metastatic sites of NSCLC that are in line with prior studies concerning evaluation of the presence of ALK abnormalities in such patients. However, they showed that assessment of ALK by IHC and FISH methods in CNS tissues require additional standardizations.
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, 20-954, Poland.|Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, 02-091, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Nicoś
authors.affiliation: Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Lublin, 20-954, Poland.
authors.forename: Bożena
authors.initials: B
authors.lastname: Jarosz
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, 20-954, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krawczyk
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, 20-954, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Wojas-Krawczyk
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, 20-954, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kucharczyk
authors.affiliation: Department of Thoracic Surgery, Medical University of Lublin, Lublin, 20-954, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sawicki
authors.affiliation: Department of Pathology, Specialist Pulmonary Hospital of Sokolowski, Zakopane, 34-500, Poland.
authors.forename: Juliusz
authors.initials: J
authors.lastname: Pankowski
authors.affiliation: Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Lublin, 20-954, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Trojanowski
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, 20-954, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Milanowski
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D055088:Early Detection of Cancer; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010363:Pattern Recognition, Automated; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016707:Tissue Fixation
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK rearrangement; CNS metastases; FISH; IHC; NSCLC