Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2010 Sep;99(2):155-63.
doi: 10.1007/s11060-010-0297-3. Epub 2010 Jul 4.

Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group

Ian F Pollack  1 , Ronald L Hamilton, Peter C Burger, Daniel J Brat, Marc K Rosenblum, Geoffrey H Murdoch, Marina N Nikiforova, Emiko J Holmes, Tianni Zhou, Kenneth J Cohen, Regina I Jakacki; Children's Oncology Group
Affiliations
Comparative Study

Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group

Ian F Pollack et al. J Neurooncol. 2010 Sep.

Abstract

Aberrant activation of Akt is a common finding in adult malignant gliomas, resulting in most cases from mutations or deletions involving PTEN, which allows constitutive Akt phosphorylation. In contrast, we have previously reported that pediatric malignant gliomas, which are morphologically similar to lesions arising in adults, have a substantially lower incidence of genomic alterations of PTEN. The objective of this study was to determine whether Akt activation was also an uncommon finding in childhood malignant gliomas and whether this feature was associated with survival. To address this issue, we examined the frequency of Akt activation, determined by overexpression of the activated phosphorylated form of Akt (Se(473)) on immunohistochemical analysis, in a series of 53 childhood malignant gliomas obtained from newly diagnosed patients treated on the Children's Oncology Group ACNS0126 and 0423 studies. The relationship between Akt activation and p53 overexpression, MIB1 labeling, and tumor histology was evaluated. The association between Akt activation and survival was also assessed. Overexpression of activated Akt was observed in 42 of 53 tumors, far in excess of the frequency of PTEN mutations we have previously observed. There was no association between Akt activation and either histology, p53 overexpression, or MIB1 proliferation indices. Although tumors that lacked Akt overexpression had a trend toward more favorable event-free survival and overall survival (p = 0.06), this association reflected that non-overexpressing tumors were significantly more likely to have undergone extensive tumor removal, which was independently associated with outcome. Activation of Akt is a common finding in pediatric malignant gliomas, although it remains uncertain whether this is an independent adverse prognostic factor. In view of the frequency of Akt activation, the evaluation of molecularly targeted therapies that inhibit this pathway warrants consideration for these tumors.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Pediatric malignant gliomas exhibiting positive (left) and negative (right) staining for pAkt
Fig. 2
Fig. 2
Event-free survival in pediatric malignant gliomas exhibiting positive and negative staining for pAkt
Fig. 3
Fig. 3
Overall survival in pediatric malignant gliomas exhibiting positive and negative staining for pAkt
Fig. 4
Fig. 4
Event-free survival in patients with 90% extent of resection exhibiting positive and negative staining for pAkt
Fig. 5
Fig. 5
Overall survival in patients with 90% extent of resection exhibiting positive and negative staining for pAkt
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Pollack IF. Current concepts: brain tumors in children. N Engl J Med. 1994;331:1500–1507. - PubMed
    1. Pollack IF, Hamilton RL, James CD, Finkelstein SD, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL. Rarity of PTEN deletions and EGFR amplification in malignant gliomas of childhood: results from the Children’s Cancer Group 945 cohort. J Neurosurg Pediatr. 2006;105:3431–3437. - PubMed
    1. Sung T, Miller DC, Hayes RL, Alonso M, Yee H, Newcomb EW. Preferential inactivation of the p53 tumor suppressor pathway and lack of EGFR amplification distinguish de novo high grade pediatric astrocytomas from de novo adult astrocytomas. Brain Pathol. 2000;10:249–259. - PMC - PubMed
    1. Bredel M, Pollack IF, Hamilton RL, James CD. Epidermal growth factor receptor (EGFR) expression and gene amplification in high-grade non-brainstem gliomas of childhood. Clin Cancer Res. 1999;5:1786–1792. - PubMed
    1. Cheng Y, Ng H-K, Zhang S-F, Ding M, Pang JC-S, Zheng J, Poon W-S. Genetic alterations in pediatric high-grade astrocytomas. Hum Pathol. 1999;30:1284–1290. - PubMed

Publication types

MeSH terms