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

• Lee JW
• Park SH
• Kang HJ
• Park KD
• Shin HY
• Ahn HS

• KMID: 2411138
• DOI: http://doi.org/10.4143/crt.2016.577

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

Figure

• 

  Fig. 1. Summary of clinical and molecular characteristics. Stages, results of molecular study and clinical outcomes were summarized. ALK, anaplastic lymphoma kinase; ATRX, alpha thalassemia/mental retardation syndrome X-linked; TERT, telomerase reverse transcriptase; INSS, International Neuroblastoma Staging System.

• 

  Fig. 2. Representative photographs of immunohistochemical staining. Photographs of slides with anaplastic lymphoma kinase positivity (A), loss of nuclear alpha thalassemia/mental retardation syndrome X-linked protein (B), and telomerase reverse transcriptase positivity (C) were illustrated.

• 

  Fig. 3. Association of anaplastic lymphoma kinase (ALK) expression with relapse rate. (A) The relapse rate was significantly higher in ALK+ patients compared with ALK– patients. (B) The relapse rate of ALK+ patients tended to be higher compared with that of ALK– patients with stage III-IV disease.

• 

  Fig. 4. Association of telomerase reverse transcriptase (TERT) expression with relapse rate. The relapse rate was slightly higher in TERT– patients compared with TERT+ patients, but this was not statistically significant. (A) All patients. (B) Stage III-IV patients.

Reference

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