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


RESULTS
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).


CONCLUSIONS
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.
Matsutani
Tomoo
T
Department of Neurological Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8670, Japan.
Nagai
Yuichiro
Y
Mine
Seiichiro
S
Murai
Hisayuki
H
Saeki
Naokatsu
N
Iwadate
Yasuo
Y
D000328:Adult; D000367:Age Factors; D001254:Astrocytoma / Q000175:diagnosis* / Q000201:enzymology* / Q000503:physiopathology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000503:physiopathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000175:diagnosis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000201:enzymology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000378:metabolism
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt