title: Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer.
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.
authors.affiliation: Department of Pathology, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Malinowsky
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Nitsche
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: K-P
authors.initials: KP
authors.lastname: Janssen
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: F G
authors.initials: FG
authors.lastname: Bader
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Späth
authors.affiliation: Department of Pathology, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Drecoll
authors.affiliation: Department of Pathology, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Keller
authors.affiliation: 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.
authors.forename: H
authors.initials: H
authors.lastname: Höfler
authors.affiliation: Department of Pathology, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.affiliation: Department of Pathology, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: K-F
authors.initials: KF
authors.lastname: Becker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D053492:Elafin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D053492:Elafin; C506806:PI3 protein, human; D051057:Proto-Oncogene Proteins c-akt