title: Clinical impact and network of determinants of tumour necrosis in colorectal cancer.
abstract: The disease outcome in colorectal cancer (CRC) can vary in a wide range within the same tumour stage. The aim of this study was to clarify the prognostic value and the determinants of tumour necrosis in CRC.
  
  
  
  The areal proportion (%) of tumour tissue showing coagulative necrosis was evaluated in a cohort of 147 CRC patients and correlated with basic clinicopathological characteristics, microvascular density (MVD), cell proliferation rate, KRAS and BRAF mutations, and survival. To validate the prognostic significance of tumour necrosis, an independent cohort of 418 CRC patients was analysed.
  
  
  
  Tumour necrosis positively correlated with tumour stage (P=8.5E-4)-especially with T class (4.0E-6)-and inversely correlated with serrated histology (P=0.014), but did not significantly associate with cell proliferation rate, MVD, and KRAS or BRAF mutation. Abundant (10% or more) tumour necrosis associated with worse disease-free survival independent of stage and other biological or clinicopathological characteristics in both cohorts, and the adverse effect was directly related to its extent. High CD105 MVD was also a stage independent marker for worse disease-free survival.
  
  
  
  Tumour necrosis percentage is a relevant histomorphological prognostic indicator in CRC. More studies are needed to disclose the mechanisms of tumour necrosis.
authors.affiliation: Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, Oulu 90014, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Väyrynen
authors.affiliation: Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, Oulu 90014, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland.
authors.forename: Juha P
authors.initials: JP
authors.lastname: Väyrynen
authors.affiliation: Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland.|Department of Surgery, Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, POB 5000, Oulu 90014, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Klintrup
authors.affiliation: Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland.|Department of Surgery, Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, POB 5000, Oulu 90014, Finland.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Mäkelä
authors.affiliation: Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, Oulu 90014, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland.
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
authors.affiliation: Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, Oulu 90014, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Tuomisto
authors.affiliation: Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, Oulu 90014, Finland.|Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Mäkinen
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D006801:Humans; D055806:Microvessels; D009154:Mutation; D009336:Necrosis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)