High expression of the wild type of Alk gene is associated with favorable prognosis in human neuroblastomas

Abstract EN

Anaplastic lymphoma kinase (ALK) gene is a transmembrane receptor tyrosine kinase initially discovered as part of the NPM-ALK fusion protein, resulting from a chromosomal rearrangement frequently associated with anaplastic large cell lymphomas.

ALK is a novel dependence receptor and normally expressed in the developing and adult nervous system.

The mutated ALK gene has been identified as a potential oncogene in human neuroblastomas (NBLs).

However, the frequency of mutation is only 5-8%.

Purpose: The present study was performed to examine the level of ALK mRNA gene expression in primary neuroblastoma patient tumor tissue samples and to assess the relation between ALK gene expression and other previously reported prognostic factors of neuroblastoma.

Methods: Quantitative real-time RT-PCR was applied to examine the expression level of ALK mRNA, and its prognostic value in primary neuroblastoma patients was analyzed by the statistical methods.

Immunohistochemical staining was used to check the expression level of ALK proteins.

Results: In analysis of 79 patients with sporadic primary neuroblastoma, we found that high expression level of ALK mRNA was significantly associated with Shimada's pathological classification (p=0.0000), patient's age (p=0.0000), MYCN amplification status (p=0.0000), tumor stage (p=0.0000) and TrkA expression level (p=0.0390), all these factors are known to be associated with good prognosis in neuroblastoma.

Of interest, immunohistochemical study revealed positive ALK in ALK-amplified tissues and cell lines.

Furthermore, mutation results showed that ALK mutation represented about 4.6% of cases and ALK amplification represented about 1.5% of cases.

So that mutations not only occur among unfavorable cases with low ALK but also in favorable cases with high ALK expression.

Conclusion: Our findings suggested that, high expression of wild type ALK is associated with good prognosis of NBL and that, as the mutation and amplification of ALK are reported to play an important role in NBL, also the expression level of wild type ALK gene might also have some function in cell growth as well as differentiation in neuroblastoma.