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Malinowsky, K.* ; Nitsche, U.* ; Janssen, K.P.* ; Bader, F.G.* ; Späth, C.* ; Drecoll, E.* ; Keller, G.* ; Höfler, H. ; Slotta-Huspenina, J.* ; Becker, K.F.*

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

Br. J. Cancer 110, 2081-2089 (2014)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Colon Cancer ; Biomarker ; Reverse-phase Protein Array ; Pi3k ; Akt ; Prognosis ; Survival; Phase Protein Microarrays; Paraffin-embedded Tissues; Growth-factor Receptor; Colorectal-cancer; Rectal-cancer; T-stage; N-stage; Survival; Recommendations; Statistics
ISSN (print) / ISBN 0007-0920
e-ISSN 1532-1827
Journal British Journal of Cancer BJC
Quellenangaben Volume: 110, Issue: 8, Pages: 2081-2089 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)