Cancer Res Treat.  2018 Apr;50(2):495-505. 10.4143/crt.2016.577.

ALK Protein Expression Is Related to Neuroblastoma Aggressiveness But Is Not Independent Prognostic Factor

Affiliations
  • 1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 2Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. shparknp@snu.ac.kr
  • 3Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. hyshin@snu.ac.kr

Abstract

PURPOSE
In this study, anaplastic lymphoma kinase (ALK) mutation and amplification, ALK protein expression, loss of the nuclear alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein, and telomerase reverse transcriptase (TERT) protein expressionwere studied to investigate potential correlations between these molecular characteristics and clinical features or outcomes in neuroblastoma.
MATERIALS AND METHODS
Seventy-two patients were enrolled in this study. Polymerase chain reaction amplification and direct sequencing were used for mutation analysis. ALK and MYCN amplifications were detected by fluorescence in situ hybridization. Protein expressionwas evaluated by immunohistochemical (IHC) staining.
RESULTS
ALK mutation was found in only two patients (4.1%); ALK amplification was not detected. ALK positivity, loss of nuclear ATRX protein, TERT positivity by IHC were detected in 40 (55.6%), nine (13.0%), and 42 (59.2%) patients, respectively. The incidence of ALK expression increased in accordance with increasing tumor stage (p=0.001) and risk group (p < 0.001). The relapse rate was significantly higher in ALK+ patients compared to that of other patients (47.5% vs. 11.3%, p=0.007). However, there was no significant difference in relapse rate when the survival analysis was confined to the high-risk patients.
CONCLUSION
Although ALK mutation was rare and no amplification was observed, ALK protein expression was found in a significant number of patients and was correlated with advanced stage and high-risk neuroblastoma. ALK protein expression could be considered as a marker related to the aggressive neuroblastoma, but it was not the independent prognostic factor for the outcome.

Keyword

Neuroblastoma; Anaplastic lymphoma kinase; Immunohistochemistry; Telomere

MeSH Terms

Fluorescence
Humans
Immunohistochemistry
In Situ Hybridization
Incidence
Lymphoma
Neuroblastoma*
Phosphotransferases
Polymerase Chain Reaction
Recurrence
Telomerase
Telomere
Phosphotransferases
Telomerase
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