PMID- 27879019
OWN - NLM
STAT- MEDLINE
DCOM- 20180731
LR  - 20210904
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 28
IP  - 1
DP  - 2018 Jan
TI  - Screening for ALK abnormalities in central nervous system metastases of 
      non-small-cell lung cancer.
PG  - 77-86
LID - 10.1111/bpa.12466 [doi]
AB  - 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; chi(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.
CI  - (c) 2016 International Society of Neuropathology.
FAU - Nicos, Marcin
AU  - Nicos M
AD  - Department of Pneumonology, Oncology and Allergology, Medical University of 
      Lublin, Lublin, 20-954, Poland.
AD  - Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, 
      02-091, Poland.
FAU - Jarosz, Bozena
AU  - Jarosz B
AD  - Department of Neurosurgery and Pediatric Neurosurgery, Medical University of 
      Lublin, Lublin, 20-954, Poland.
FAU - Krawczyk, Pawel
AU  - Krawczyk P
AD  - Department of Pneumonology, Oncology and Allergology, Medical University of 
      Lublin, Lublin, 20-954, Poland.
FAU - Wojas-Krawczyk, Kamila
AU  - Wojas-Krawczyk K
AD  - Department of Pneumonology, Oncology and Allergology, Medical University of 
      Lublin, Lublin, 20-954, Poland.
FAU - Kucharczyk, Tomasz
AU  - Kucharczyk T
AD  - Department of Pneumonology, Oncology and Allergology, Medical University of 
      Lublin, Lublin, 20-954, Poland.
FAU - Sawicki, Marek
AU  - Sawicki M
AD  - Department of Thoracic Surgery, Medical University of Lublin, Lublin, 20-954, 
      Poland.
FAU - Pankowski, Juliusz
AU  - Pankowski J
AD  - Department of Pathology, Specialist Pulmonary Hospital of Sokolowski, Zakopane, 
      34-500, Poland.
FAU - Trojanowski, Tomasz
AU  - Trojanowski T
AD  - Department of Neurosurgery and Pediatric Neurosurgery, Medical University of 
      Lublin, Lublin, 20-954, Poland.
FAU - Milanowski, Janusz
AU  - Milanowski J
AD  - Department of Pneumonology, Oncology and Allergology, Medical University of 
      Lublin, Lublin, 20-954, Poland.
LA  - eng
PT  - Journal Article
DEP - 20170302
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anaplastic Lymphoma Kinase
MH  - Carcinoma, Non-Small-Cell Lung/enzymology/genetics/*pathology
MH  - Central Nervous System Neoplasms/*enzymology/genetics/pathology/*secondary
MH  - Early Detection of Cancer
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - Image Interpretation, Computer-Assisted
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/enzymology/genetics/*pathology
MH  - Male
MH  - Middle Aged
MH  - Pattern Recognition, Automated
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Tissue Fixation
PMC - PMC8028499
OTO - NOTNLM
OT  - ALK rearrangement
OT  - CNS metastases
OT  - FISH
OT  - IHC
OT  - NSCLC
COIS- The authors declare no conflict of interest.
EDAT- 2016/11/24 06:00
MHDA- 2018/08/01 06:00
PMCR- 2017/03/02
CRDT- 2016/11/24 06:00
PHST- 2016/08/12 00:00 [received]
PHST- 2016/11/22 00:00 [accepted]
PHST- 2016/11/24 06:00 [pubmed]
PHST- 2018/08/01 06:00 [medline]
PHST- 2016/11/24 06:00 [entrez]
PHST- 2017/03/02 00:00 [pmc-release]
AID - BPA12466 [pii]
AID - 10.1111/bpa.12466 [doi]
PST - ppublish
SO  - Brain Pathol. 2018 Jan;28(1):77-86. doi: 10.1111/bpa.12466. Epub 2017 Mar 2.