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

Karagkounis, G.; Stranjalis, George; Argyrakos, Theodoros; Pantelaion, Varvara; Mastoris, Konstantinos; Rontogianni, Dimitra; Komaitis, Spyridon; Κalamatianos, Theodosis; Sakas, Damianos E.; Tiniakos, Dina

doi:10.1136/jclinpath-2016-204102

Cited by 16 publications

(25 citation statements)

References 37 publications

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“…In the present study, high ALK-1 expression showed a significant association with male sex, however, no significant relation between ALK-1 expression and patient's age. These findings are not matched with the study done by Karagkounis et al [5], which reported that ALK overexpression is more common in older individuals (> 59 years) and that was no association between ALK expression and patient's sex. This discrepancy was due to division of their cases into subgroups according to IDH1 protein expression with cutoff median age of 59 years, which was not implemented in the current study.…”

Section: Discussioncontrasting

confidence: 99%

“…ALK-1 positivity was identified as a brown cytoplasmic expression. A four-tier scoring system was used for evaluation of ALK-1 positivity [5]; score 1 was corresponded to weak cytoplasmic expression of ALK-1, moderate cytoplasmic expression was considered as score 2, and strong cytoplasmic expression was considered as score 3 (Fig. 1).…”

Section: Evaluation Of Alk-1 and H-tert Ihc Expressionmentioning

confidence: 99%

“…Some studies showed that negative ALK-1 expression in GBM predicted better overall survival (OS) [4]. Other studies revealed no significant impact on OS with different ALK expression levels in GBM [5].…”

mentioning

confidence: 99%

“…ALK gene rearrangements are mostly linked to subcellular changes in the ALK protein, which can assessed by immunohistochemistry (IHC) and can likewise be evaluated with the fluorescence in situ hybridization (FISH) technique with higher sensitivity and specificity [5]. Both tests use an in vitro diagnostic assay that the Food and Drug Administration (FDA) approved for crizotinib response prediction.…”

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confidence: 99%

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Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations

Elsers

Temerik

Attia

et al. 2021

J Pathol Transl Med

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Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM). Methods: The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry. Results: Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS. Conclusions: High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.

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Section: Discussioncontrasting

confidence: 99%

Section: Evaluation Of Alk-1 and H-tert Ihc Expressionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations

Elsers

Temerik

Attia

et al. 2021

J Pathol Transl Med

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“…It is a highly hypoxic tumor, which is resistant to conventional chemotherapy or radiotherapy, and of poor prognosis [ 126 ]. ALK overexpression, without ALK gene amplification or translocation, has been shown in human tumors [ 127 ] and in glioblastoma stem cell lines (GSCs) [ 128 ], and ALK signaling has been associated with GSC self-renewal and tumor survival [ 129 ]. Recently, ALK signaling was shown to confer GBMs proliferative advantages through neovascularization [ 130 ].…”

Section: Alk-associated Cancersmentioning

confidence: 99%

Targeting Autophagy in ALK-Associated Cancers

Frentzel

Sorrentino

Giuriato

2017

Cancers

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Autophagy is an evolutionarily conserved catabolic process, which is used by the cells for cytoplasmic quality control. This process is induced following different kinds of stresses e.g., metabolic, environmental, or therapeutic, and acts, in this framework, as a cell survival mechanism. However, under certain circumstances, autophagy has been associated with cell death. This duality has been extensively reported in solid and hematological cancers, and has been observed during both tumor development and cancer therapy. As autophagy plays a critical role at the crossroads between cell survival and cell death, its involvement and therapeutic modulation (either activation or inhibition) are currently intensively studied in cancer biology, to improve treatments and patient outcomes. Over the last few years, studies have demonstrated the occurrence of autophagy in different Anaplastic Lymphoma Kinase (ALK)-associated cancers, notably ALK-positive anaplastic large cell lymphoma (ALCL), non-small cell lung carcinoma (NSCLC), Neuroblastoma (NB), and Rhabdomyosarcoma (RMS). In this review, we will first briefly describe the autophagic process and how it can lead to opposite outcomes in anti-cancer therapies, and we will then focus on what is currently known regarding autophagy in ALK-associated cancers.

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cMyc and ERK activity are associated with resistance to ALK inhibitory treatment in glioblastoma

et al. 2019

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

Abstract: 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.

Cited by 16 publications

References 37 publications

Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations

Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations

Targeting Autophagy in ALK-Associated Cancers

cMyc and ERK activity are associated with resistance to ALK inhibitory treatment in glioblastoma

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