Evaluation of Immunohistochemical Expression of ALK-1 in Gliomas, WHO Grade 4 and Its Correlation with IDH1-R132H Mutation Status.

Abstract

Glioblastoma (GB), a grade 4 glioma is the most common primary malignant brain tumor in adults. Recently, the mutation status of isocitrate dehydrogenase (IDH) has been crucial in the treatment of GB. IDH mutant cases display a more favorable prognosis than IDH-wild type ones. The anaplastic lymphoma kinase (ALK) is expressed as a receptor tyrosine kinase in both the developing central and peripheral nervous systems. Increasing lines of evidence suggest that ALK is over-expressed in GB and represents a potential therapeutic target. The goal of the current study was to investigate ALK-1 immunohistochemical expression in gliomas, grade 4, besides its correlation with IDH1-R132H mutation status and the clinicopathological parameters of the tumors. Seventy cases of gliomas, grade 4 were tested for immunohistochemical expression of ALK-1 & IDH1-R132H in the tumor cells. ALK-1 immunoexpression was detected in 22.9% of our cases and IDH1-R132H mutation was detected in 12.9% of them. ALK-1 expression (100%) was only detected in the more aggressive IDH R132H-negative GBs. ALK-1 expression was also noted in the larger-sized tumors, more in males and patients older than the mean age. Conclusion: Our results suggest that mutations in ALK-1 may predict a more dismal prognosis since ALK expression was only noted in IDH-R132H negative GBs known to have a considerably poorer outcome compared to IDH-R132H mutant cases. GBs with detectable ALK-protein expression could potentially experience substantial clinical advantages through the utilization of newly introduced ALK inhibitors allowing personalized treatment to a subset of patients. Hence, future studies targeting ALK in IDH wildtype Glioblastomas including clinical trials on larger scales are recommended.