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Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome
  1. George Karagkounis1,
  2. George Stranjalis2,
  3. Theodore Argyrakos1,
  4. Varvara Pantelaion1,
  5. Konstantinos Mastoris1,
  6. Dimitra Rontogianni1,
  7. Spyridon Komaitis2,
  8. Theodosis Kalamatianos2,
  9. Damianos Sakas2,
  10. Dina Tiniakos3,4
  1. 1Department of Pathology, Evaggelismos Hospital, Athens, Greece
  2. 2Department of Neurosurgery, Medical School, National and Kapodistrian University of Athens, Evaggelismos Hospital, Athens, Greece
  3. 3Medical School, National and Kapodistrian University of Athens, Athens, Greece
  4. 4Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University & Newcastle Molecular Pathology Node, Newcastle upon Tyne, UK
  1. Correspondence to Dr Dina Tiniakos, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, William Leech Building, 4th Floor, Room M4-143, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; dina.tiniakos{at}newcastle.ac.uk

Abstract

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)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 multiple alk 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). 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 underlying alk gene amplification. Despite being more common in rapidly growing, clinically aggressive GBM, ALK overexpression did not show correlation with prognosis in this study.

  • P53
  • KI 67
  • CENTRAL NERVE SYSTEM

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Footnotes

  • Handling editor Cheok Soon Lee

  • Contributors GK: Drafting, revising, acquisition analysis and interpretation of data. GS: Critically revising. TA: Conception and design, acquisition of data, drafting. VP: Acquisition of data. KM: Acquisition of data. DR: Critically revising. SK: Acquisition of data. TK Acquisition of data, drafting and critically revising. DS: Critically revising. DT: Drafting, critically revising, final approval.

  • Competing interests None declared.

  • Ethics approval National and Kapodistrian University of Athens, Medical School Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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