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Screening for ALK abnormalities in central nervous system metastases of non-small-cell lung cancer
Marcin Nicoś1,2, Bożena Jarosz3, Paweł Krawczyk1
1Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, 20-954, Poland.
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.
Insights
Anaplastic lymphoma kinase (ALK) gene rearrangement occurs in 4.8% of non-small-cell lung cancer (NSCLC) central nervous system metastases. ALK abnormalities were more frequent in former smokers, and testing methods require standardization for CNS tissues.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anaplastic lymphoma kinase (ALK) gene rearrangement is a known driver mutation in a subset of non-small-cell lung cancer (NSCLC).
- ALK tyrosine kinase inhibitors (TKIs) demonstrate efficacy in NSCLC patients with ALK rearrangements, including those with central nervous system (CNS) metastases.
- The frequency of ALK rearrangement specifically within CNS metastases of NSCLC remains underreported.
Purpose of the Study:
- To determine the frequency of ALK gene abnormalities in CNS metastases from NSCLC.
- To investigate the association of ALK abnormalities with histopathology and smoking status in CNS metastases.
- To evaluate the concordance and challenges of ALK assessment using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in CNS tissues.
Main Methods:
- Analysis of 145 formalin-fixed paraffin-embedded (FFPE) tissue samples from NSCLC CNS metastases.
- Utilized automated immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for ALK abnormality detection.
- Correlated ALK findings with histopathological subtypes and patient smoking history.
Main Results:
- ALK abnormalities were detected in 4.8% (7/145) of NSCLC CNS metastases.
- Six of 80 adenocarcinoma (AD) samples (7.5%) showed ALK abnormalities; one adenosquamous carcinoma also harbored abnormalities.
- ALK abnormalities were significantly more frequent in former-smokers (P<0.0002).
- Discrepancies between IHC and FISH were observed, attributed to background staining in CNS tissues.
Conclusions:
- ALK gene rearrangement is present in a notable proportion of NSCLC CNS metastases.
- The assessment of ALK status in CNS metastases requires careful interpretation and standardization of IHC and FISH techniques due to tissue-specific challenges.
- Findings support the relevance of ALK alterations in the CNS metastatic setting of NSCLC.
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