Screening for ALK abnormalities in central nervous system metastases of non-small-cell lung cancer

被引:6
作者
Nicos, Marcin [1 ,2 ]
Jarosz, Bozena [3 ]
Krawczyk, Pawel [1 ]
Wojas-Krawczyk, Kamila [1 ]
Kucharczyk, Tomasz [1 ]
Sawicki, Marek [4 ]
Pankowski, Juliusz [5 ]
Trojanowski, Tomasz [3 ]
Milanowski, Janusz [1 ]
机构
[1] Med Univ Lublin, Dept Pneumonol Oncol & Allergol, Jaczewskiego 8, PL-20954 Lublin, Poland
[2] Med Univ Warsaw, Postgrad Sch Mol Med, PL-02091 Warsaw, Poland
[3] Med Univ Lublin, Dept Neurosurg & Pediat Neurosurg, PL-20954 Lublin, Poland
[4] Med Univ Lublin, Dept Thorac Surg, PL-20954 Lublin, Poland
[5] Specialist Pulm Hosp Sokolowski, Dept Pathol, PL-34500 Zakopane, Poland
关键词
ALK rearrangement; IHC; FISH; CNS metastases; NSCLC; ANAPLASTIC LYMPHOMA KINASE; EML4-ALK FUSION GENE; BRAIN METASTASES; EGFR; REARRANGEMENT; CRIZOTINIB; IMMUNOHISTOCHEMISTRY; IDENTIFICATION; ASSOCIATION; MUTATIONS;
D O I
10.1111/bpa.12466
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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; (2)=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.
引用
收藏
页码:77 / 86
页数:10
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