PMID- 28326957
OWN - NLM
STAT- MEDLINE
DCOM- 20190422
LR  - 20200228
IS  - 1093-5266 (Print)
IS  - 1093-5266 (Linking)
VI  - 20
IP  - 2
DP  - 2017 Mar-Apr
TI  - ALK Gene Copy Number Gain and Immunohistochemical Expression Status Using Three 
      Antibodies in Neuroblastoma.
PG  - 133-141
LID - 10.1177/1093526616686445 [doi]
AB  - Anaplastic lymphoma kinase ( ALK) gene aberrations-such as mutations, 
      amplifications, and copy number gains-represent a major genetic predisposition to 
      neuroblastoma (NB). This study aimed to evaluate the correlation between ALK gene 
      copy number status, ALK protein expression, and clinicopathological parameters. 
      We retrospectively retrieved 30 cases of poorly differentiated NB and constructed 
      tissue microarrays (TMAs). ALK copy number changes were assessed by fluorescence 
      in situ hybridization (FISH) assays, and ALK immunohistochemistry (IHC) testing 
      was performed using three different antibodies (ALK1, D5F3, and 5A4 clones). ALK 
      amplification and copy number gain were observed in 10% (3/30) and 53.3% (16/30) 
      of the cohort, respectively. There were positive correlations between ALK copy 
      number and IHC-positive rate in ALK1 and 5A4 antibodies ( P < 0.001 and 
      P = 0.019, respectively). ALK1, D5F3, and 5A4 antibodies equally showed 100% 
      sensitivity in detecting ALK amplification. However, the sensitivity for 
      detecting copy number gain differed among the three antibodies, with 75% 
      sensitivity in D5F3 and 0% sensitivity in ALK1. ALK-amplified NBs were correlated 
      with synchronous MYCN amplification and chromosome 1p deletion. ALK IHC 
      positivity was frequently observed in INSS stage IV and high-risk group patients. 
      In conclusion, this study identified that an increase in the ALK copy number is a 
      frequent genetic alteration in poorly differentiated NB. ALK-amplified NBs showed 
      consistent ALK IHC positivity with all kinds of antibodies. In contrast, the 
      detection performance of ALK copy number gain was antibody dependent, with the 
      D5F3 antibody showing the best sensitivity.
FAU - Kim, Eun Kyung
AU  - Kim EK
AD  - 1 Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
FAU - Kim, Sewha
AU  - Kim S
AD  - 1 Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
AD  - 2 Department of Pathology, CHA Bundang Medical Center, CHA University, 
      Gyeonggi-do, Korea.
LA  - eng
PT  - Journal Article
DEP - 20170125
PL  - United States
TA  - Pediatr Dev Pathol
JT  - Pediatric and developmental pathology : the official journal of the Society for 
      Pediatric Pathology and the Paediatric Pathology Society
JID - 9809673
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
SB  - IM
MH  - Adrenal Gland Neoplasms/*diagnosis/genetics/metabolism/pathology
MH  - Anaplastic Lymphoma Kinase/*genetics/metabolism
MH  - Biomarkers, Tumor/*genetics/metabolism
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - *Gene Dosage
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Neuroblastoma/*diagnosis/genetics/metabolism/pathology
MH  - Prognosis
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Tissue Array Analysis
OTO - NOTNLM
OT  - ALK
OT  - copy number gain
OT  - fluorescence in situ hybridization
OT  - immunohistochemistry
OT  - neuroblastoma
EDAT- 2017/03/23 06:00
MHDA- 2019/04/23 06:00
CRDT- 2017/03/23 06:00
PHST- 2017/03/23 06:00 [entrez]
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2019/04/23 06:00 [medline]
AID - 10.1177/1093526616686445 [doi]
PST - ppublish
SO  - Pediatr Dev Pathol. 2017 Mar-Apr;20(2):133-141. doi: 10.1177/1093526616686445. 
      Epub 2017 Jan 25.