The clinical and prognostic role of ALK in glioblastoma.


Journal

Pathology, research and practice
ISSN: 1618-0631
Titre abrégé: Pathol Res Pract
Pays: Germany
ID NLM: 7806109

Informations de publication

Date de publication:
May 2021
Historique:
received: 20 02 2021
revised: 08 04 2021
accepted: 09 04 2021
pubmed: 23 4 2021
medline: 23 11 2021
entrez: 22 4 2021
Statut: ppublish

Résumé

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). 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. 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). 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 33887544
pii: S0344-0338(21)00108-4
doi: 10.1016/j.prp.2021.153447
pii:
doi:

Substances chimiques

Biomarkers, Tumor 0
ALK protein, human EC 2.7.10.1
Anaplastic Lymphoma Kinase EC 2.7.10.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

153447

Informations de copyright

Copyright © 2021 Elsevier GmbH. All rights reserved.

Auteurs

Enrico Franceschi (E)

Department of Oncology, AUSL Bologna, Bologna, Italy. Electronic address: enricofra@yahoo.it.

Dario De Biase (D)

Department of Pharmacy and Biotechnology (FaBIT) - Molecular Pathology Laboratory, University of Bologna, Bologna, Italy.

Vincenzo Di Nunno (V)

Department of Oncology, AUSL Bologna, Bologna, Italy.

Annalisa Pession (A)

Department of Pharmacy and Biotechnology (FaBIT) - Molecular Pathology Laboratory, University of Bologna, Bologna, Italy.

Alicia Tosoni (A)

Department of Oncology, AUSL Bologna, Bologna, Italy.

Lidia Gatto (L)

Department of Oncology, AUSL Bologna, Bologna, Italy.

Giovanni Tallini (G)

Molecular Diagnostic Unit, University of Bologna School of Medicine and Surgery, Bologna, Italy.

Michela Visani (M)

Molecular Diagnostic Unit, University of Bologna School of Medicine and Surgery, Bologna, Italy.

Raffaele Lodi (R)

IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy.

Stefania Bartolini (S)

Department of Oncology, AUSL Bologna, Bologna, Italy.

Alba Ariela Brandes (AA)

Department of Oncology, AUSL Bologna, Bologna, Italy.

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Classifications MeSH