Introduction
Neuroblastoma is an embryonal tumor originating from the autonomic
nervous system with a heterogeneous clinical and biological
spectrum.1 There is a wide range of clinical outcomes
from spontaneous regression or maturation to relentless progression
leading to death despite extensive multimodal
therapies.1-3 As per the International Neuroblastoma
Risk Group (INRG) Task Force, age and stage at presentation, histologic
category based on tumor differentiation and mitotic karyorrhectic index
(MKI), DNA ploidy, MYCN amplification, and chromosome 11q status
are parameters required for better risk stratification into very low,
low, intermediate and high-risk groups.4 Patients are
managed according to their risk groups however the outcome for high-risk
neuroblastoma patients remain poor, with overall 5-year survival below
50%.4-5
Anaplastic lymphoma kinase (ALK ) gene and the corresponding
protein ALK are important players in embryonic neural development and
are highly expressed in that context.6 The biological
role of ALK in neuroblastoma has been studied in neuroblastoma
cell lines.7 The discovery of activating mutations in
the tyrosine kinase domain of ALK as the major cause of
hereditary neuroblastoma provides the first example of a pediatric
cancer arising from germline mutations in an
oncogene.8 The role of MYCN in neuroblastoma is well
established and evaluation of MYCN amplification in tissue
samples is an important aspect of current risk stratification protocols
including the INRG and COG algorithms for
management.4,9 Interestingly both genes are just 13.2
MB apart on chromosome 2p. ALK, as a therapeutic target in primary
neuroblastoma, represents a major research advance in this childhood
cancer.10 There have been a few studies on ALK protein
expression in neuroblastoma by
immunohistochemistry. 11-14 However, its utility as an
independent prognostic marker and correlation to traditional prognostic
markers such as age, tumor morphology, and MYCN amplification are
still not well established and hence this was the main aim of this
study. We also evaluated a subset of cases for ALK gene mutation
by next generation sequencing to determine its frequency and have
demonstrated its feasibility using fine needle aspiration biopsy
samples.