title: Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome.
abstract: OBJECTIVE
  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)R132H-negative and 5 IDH-mutant (IDH1R132H-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 multiplealkgene 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). IDH1R132H-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 underlyingalkgene amplification. Despite being more common in rapidly growing, clinically aggressive GBM, ALK overexpression did not show correlation with prognosis in this study.
authors.affiliation: Department of Pathology, Evaggelismos Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Karagkounis
authors.affiliation: Department of Neurosurgery, Medical School, National and Kapodistrian University of Athens, Evaggelismos Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Stranjalis
authors.affiliation: Department of Pathology, Evaggelismos Hospital, Athens, Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Argyrakos
authors.affiliation: Department of Pathology, Evaggelismos Hospital, Athens, Greece.
authors.forename: Varvara
authors.initials: V
authors.lastname: Pantelaion
authors.affiliation: Department of Pathology, Evaggelismos Hospital, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mastoris
authors.affiliation: Department of Pathology, Evaggelismos Hospital, Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Rontogianni
authors.affiliation: Department of Neurosurgery, Medical School, National and Kapodistrian University of Athens, Evaggelismos Hospital, Athens, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Komaitis
authors.affiliation: Department of Neurosurgery, Medical School, National and Kapodistrian University of Athens, Evaggelismos Hospital, Athens, Greece.
authors.forename: Theodosis
authors.initials: T
authors.lastname: Kalamatianos
authors.affiliation: Department of Neurosurgery, Medical School, National and Kapodistrian University of Athens, Evaggelismos Hospital, Athens, Greece.
authors.forename: Damianos
authors.initials: D
authors.lastname: Sakas
authors.affiliation: Medical School, National and Kapodistrian University of Athens, Athens, Greece.|Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University & Newcastle Molecular Pathology Node, Newcastle upon Tyne, UK.
authors.forename: Dina
authors.initials: D
authors.lastname: Tiniakos
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D049109:Cell Proliferation; D005260:Female; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: CENTRAL NERVE SYSTEM; KI 67; P53