The clinical and prognostic role of ALK in glioblastoma.

Abstract Background anaplastic lymphoma kinase (ALK) overexpression and gene alterations have been detected in several malignancies, with prognostic and therapeutic implications. However, few studies investigated the correlation between ALK altered expression and prognosis in patients with glioblastoma (GBM). Methods We performed an evaluation of ALK overexpression and structural/quantitative chromosome alterations through immune-histochemical assay (IHC with D5F3 antibody) and fluorescent in situ hybridization (FISH) in patients with isocitrate dehydrogenase (IDH) wild type (wt) GBM. Assuming an ALK overexpression in 20 % of patients we planned a sample of 44 patients to achieve a probability of 90 % to include from 10 % to 30 % of patients with ALK alterations. Results We evaluated 44 patients with IDH wt GBM, treated in our institution and dead due to GBM progression in 2017. ALK overexpression obtained by a composed score (the product of IHC intensity staining and rate of positive cells) was observed in 19 (43 %) patients. FISH analysis showed that 11 patients (25 %) had gene deletion, 2 patients (4.5 %) had monosomy and one patient (2.3 %) presented polysomy. Only one patient (2.3 %) demonstrated ALK rearrangement. There was no statistical difference in median OS between patients with ALK-positive (mOS = 18.9 months) and ALK-negative IHC (mOS = 18.0 months). Conclusion We identified some rare previously unreported alterations of ALK gene in patients with IDH wt GBM. In these patients, the ALK overexpression does not influences survival.