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Akt/protein kinase B overexpression as an accurate prognostic marker in adult diffuse astrocytoma.

Authors: Matsutani, T  Nagai, Y  Mine, S  Murai, H  Saeki, N  Iwadate, Y 
Citation: Matsutani T, etal., Acta Neurochir (Wien). 2009 Mar;151(3):263-8; discussion 268. Epub 2009 Feb 25.
Pubmed: (View Article at PubMed) PMID:19240976
DOI: Full-text: DOI:10.1007/s00701-009-0199-3

BACKGROUND: Akt/Protein kinase B (PKB) is a common downstream molecule of Ras signaling essential for cell survival. In an attempt to find a novel prognostic marker of diffuse astrocytoma, we performed an immunohistochemical analysis of Akt/PKB with regard to patient survival and regrowth patterns. METHODS: Twenty-four adult patients with diffuse astrocytoma were similarly managed without early post-operative radiotherapy and followed up for a median period of 7.5 years. They were analysed by immunohistochemistry for Akt/PKB expression as well as p53 protein accumulation, epidermal growth factor receptor (EGFR) expression, and MIB-1 labeling index. The prognostic significance of each molecular covariate was tested by multivariate analysis using Cox's proportional hazard model including age, performance status, and extent of surgical resection. FINDINGS: Akt/PKB overexpression significantly correlated with both shorter overall survival (OS) and progression-free survival (PFS) (p = 0.0110). All the Akt/PKB-positive patients with post-operative residual tumours experienced tumour recurrences, whereas only a small fraction of the Akt/PKB-negative individuals had recurrences (p = 0.0070). Invasive recurrence into surrounding brain occurred only in the Akt/PKB-overexpressed tumours. In contrast, MIB-1 labeling index correlated only with OS, while p53 protein accumulation correlated only with PFS. The Cox's proportional hazard model identified Akt/PKB overexpression as a significant prognostic factor for shorter PFS (p = 0.0117). CONCLUSION: These results show that Akt/PKB overexpression would be suggestive of malignant progression and invasive regrowth of diffuse astrocytoma, and it can serve as a novel prognostic marker for this tumour.


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CRRD Object Information
CRRD ID: 5509079
Created: 2011-10-27
Species: All species
Last Modified: 2011-10-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.