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.