title: Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at risk for recurrence is an unmet clinical need. KCNQ1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with CRC liver metastases. In this study the prognostic value of KCNQ1 in stage II and stage III colon cancer patients was examined.
  
  
  METHODS
  KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. Subsequently, KCNQ1 protein expression was evaluated in an independent cohort of 386 stage II and stage III colon cancer patients by immunohistochemistry of tissue microarrays.
  
  
  RESULTS
  Low KCNQ1 mRNA expression in stage II microsatellite stable (MSS) colon cancers was associated with poor disease-free survival (DFS) (P=0.025). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in stage II MSS (P<0.0001), stage III MSS (P=0.0001) and stage III microsatellite instable colon cancers (P=0.041). KCNQ1 seemed an independent prognostic value in addition to other high-risk parameters like angio-invasion, nodal stage and microsatellite instability-status.
  
  
  CONCLUSIONS
  We conclude that KCNQ1 is a promising biomarker for prediction of disease recurrence and may aid stratification of patients with stage II MSS colon cancer for adjuvant chemotherapy.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam 1081HV, The Netherlands.|Department of Surgery, Spaarne Gasthuis, Haarlem 2035RC, The Netherlands.
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: den Uil
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam 1081HV, The Netherlands.
authors.forename: Veerle M H
authors.initials: VM
authors.lastname: Coupé
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam 1100DD, The Netherlands.
authors.forename: Janneke F
authors.initials: JF
authors.lastname: Linnekamp
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam 1081HV, The Netherlands.|Department of Pathology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.
authors.forename: Evert
authors.initials: E
authors.lastname: van den Broek
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam 1081HV, The Netherlands.
authors.forename: Jeroen A C M
authors.initials: JA
authors.lastname: Goos
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam 1081HV, The Netherlands.|Department of Pathology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.
authors.forename: Pien M
authors.initials: PM
authors.lastname: Delis-van Diemen
authors.affiliation: Department of Surgery, Albert Schweitzer Hospital, Dordrecht 3300AK, The Netherlands.
authors.forename: Eric J Th
authors.initials: EJ
authors.lastname: Belt
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam 1081HV, The Netherlands.
authors.forename: Nicole C T
authors.initials: NC
authors.lastname: van Grieken
authors.affiliation: Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, Minnesota, MN 55812, USA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Scott
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam 1100DD, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Vermeulen
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam 1100DD, The Netherlands.
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
authors.affiliation: Department of Pathology, Spaarne Gasthuis, Haarlem 2035RC, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Bril
authors.affiliation: Department of Surgery, Spaarne Gasthuis, Haarlem 2035RC, The Netherlands.
authors.forename: Hein B A C
authors.initials: HB
authors.lastname: Stockmann
authors.affiliation: Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, Minnesota, MN 55812, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Cormier
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam 1081HV, The Netherlands.|Department of Pathology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam 1081HV, The Netherlands.|Department of Pathology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.
authors.forename: Remond J A
authors.initials: RJ
authors.lastname: Fijneman
mesh_terms: D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D012333:RNA, Messenger