Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome.

Aims: To study anaplastic lymphoma kinase (ALK) protein expression and possible underlying gene alterations in glioblastoma (GBM), correlating them with clinical outcome.

Methods: We studied ALK immunohistochemical expression and fluorescent in situ hybridisation (FISH)-detected ALK gene alterations in 51 GBMs (46 isocitrate dehydrogenase-1 (IDH1)-negative and 5 IDH-mutant (IDH1-positive)). We compared two anti-ALK antibodies and immunohistochemical detection systems (5Α4/Nichirei Biosciences, D5F3/Ventana). The results were correlated with tumour cell proliferation and clinical outcome.

Results: Intense granular cytoplasmic ALK immunostaining was observed in 10/51 (19.61%) GBM and correlated with high Ki67 proliferation index; only 1 in 10 ALK-positive cases displayed multiple gene signals by FISH. Moderate ALK immunostaining was observed in 21 (41.17%), weak immunostaining in 5 (9.80%) while 15 (29.42%) cases were negative. p53 was expressed in 26/51 GBM (50.9%) (10% cut-off). IDH1-negative GBM showed higher ALK expression compared with IDH-mutant GBM (65.2% vs 20%). ALK overexpression was more common in older patients but did not correlate with other clinicopathological variables or patient overall survival.

Conclusions: ALK overexpression can be identified in up to 70% of GBMs and does not correlate with underlying gene amplification. Despite being more common in rapidly growing, clinically aggressive GBM, ALK overexpression did not show correlation with prognosis in this study.