ALK gene copy number gain and immunohistochemical expression status using three antibodies in neuroblastoma

Eunkyung Kim, Sewha Kim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 ¼ 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.

Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalPediatric and Developmental Pathology
Volume20
Issue number2
DOIs
Publication statusPublished - 2017 Jan 1

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Gene Dosage
Neuroblastoma
Antibodies
Immunohistochemistry
anaplastic lymphoma kinase
Chromosome Deletion
Genetic Predisposition to Disease
Fluorescence In Situ Hybridization

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

Cite this

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title = "ALK gene copy number gain and immunohistochemical expression status using three antibodies in neuroblastoma",
abstract = "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 ¼ 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.",
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ALK gene copy number gain and immunohistochemical expression status using three antibodies in neuroblastoma. / Kim, Eunkyung; Kim, Sewha.

In: Pediatric and Developmental Pathology, Vol. 20, No. 2, 01.01.2017, p. 133-141.

Research output: Contribution to journalArticle

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AU - Kim, Sewha

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