Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: Correlation with ALK gene alterations

Abstract

Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM). Methods: The current study is a retrospective study on a cohort of patients with GBM (n=53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry. Results: Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS. Conclusions: High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.