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Br J Cancer. 2014 Apr 15;110(8):2081-9. doi: 10.1038/bjc.2014.100. Epub 2014 Mar 11.

Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer.

Author information

1
Department of Pathology, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
2
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
3
1] Department of Pathology, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany [2] Department of Pathology, Helmholtz-Centre Munich, Ingolstädter Landstrasse 1, 85764 Munich, Germany.

Abstract

BACKGROUND:

Patients with UICC/AJCC stage II colon cancer have a high 5-year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. We applied reverse-phase protein arrays (RPPA) for phosphatidylinositide-3-kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery.

METHODS:

Full-length proteins were extracted from formalin-fixed, paraffin-embedded tissue samples of 118 patients who underwent curative resection. RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide-3-kinase pathway. Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel.

RESULTS:

Expression of phospho-AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho-4E-BP1 (HR=4.12; P=0.011) were prognostic factors for disease-free survival. None of the molecular genetic alterations were significantly associated with prognosis.

CONCLUSIONS:

Our data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high-risk patients.

PMID:
24619078
PMCID:
PMC3992486
DOI:
10.1038/bjc.2014.100
[Indexed for MEDLINE]
Free PMC Article

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