mRNA Expression Level of ALK in Neuroblastoma Is Associated with Histological Subtype, ALK Mutations and ALK Immunohistochemical Protein Expression

• Main Authors: Rixt S. Bruinsma (Author), Marta F. Fiocco (Author), Wendy W. J. de Leng (Author), Lennart A. Kester (Author), Karin P. S. Langenberg (Author), Godelieve A. M. Tytgat (Author), Max M. van Noesel (Author), Marc H. W. A. Wijnen (Author), Alida F. W. van der Steeg (Author), Ronald R. de Krijger (Author)
• Format: Book
• Published: MDPI AG, 2024-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<i>ALK</i> is related to poor survival in neuroblastoma patients. We investigated the prognostic relevance of <i>ALK</i> mRNA expression and the relationship with ALK immunohistochemical expression, histological subtype and <i>ALK</i> aberrations. Whole transcriptome sequencing data were available from 54 patients. Overall survival (OS) and event-free survival (EFS) were estimated with Kaplan-Meier's methodology. ALK protein expression was analyzed by immunohistochemistry. <i>ALK</i> aberrations were detected using whole exome sequencing, single nucleotide polymorphism array, next generation sequencing and/or fluorescence in situ hybridization. OS was 74.8% and EFS was 60%. <i>ALK</i> mRNA expression was not associated with OS (HR 1.127, 95% CI (0.812-1.854), <i>p</i> = 0.331) and adjusted EFS (HR 1.134, 95% CI (0.783-1.644), <i>p</i> = 0.505), but was associated with histological subtype (OR 1.914, 95% CI (1.083-3.382), <i>p</i> = 0.025) and ALK protein expression (negative versus weak: OR 2.829, 95% CI (1.290-6.204), <i>p</i> = 0.009) (negative versus moderate/strong: OR 2.934, 95% CI (0.889-9.679), <i>p</i> = 0.077). <i>ALK</i> mutated tumors had significantly higher <i>ALK</i> mRNA expression than non-mutated tumors (<i>p</i> < 0.001). <i>MYCN</i>-amplified neuroblastomas have higher <i>MYCN</i> mRNA expression (<i>p</i> ≤ 0.001), but not <i>ALK</i> mRNA expression (<i>p</i> = 0.553). <i>ALK</i> mRNA expression is higher in <i>ALK</i> mutated neuroblastomas and is associated with poorer differentiation degree and higher protein expression. <i>ALK</i> mRNA expression is not significantly associated with OS and EFS.

Item Description

10.3390/jmp5030022
2673-5261