title: Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers.
abstract: BACKGROUND
  Endostatin, a fragment of collagen XVIII, is an endogenous angiogenesis inhibitor with anti-tumour functions. However, elevated circulating endostatin concentrations have been found in several human cancers including colorectal cancer (CRC).
  
  
  METHODS
  Serum endostatin levels were measured by enzyme-linked immunoassay from a series of 143 patients with CRC and from 84 controls, and correlated with detailed clinicopathological features of CRC, serum leukocyte differential count and C-reactive protein (CRP) levels.
  
  
  RESULTS
  Patients with CRC had higher serum endostatin levels than the controls (P=0.005), and high levels associated with age, tumour invasion through the muscularis propria and poor differentiation, but not with metastases. Endostatin levels showed a positive correlation with the markers of systemic inflammatory response and a negative correlation with the densities of tumour-infiltrating mast cells and dendritic cells. Collagen XVIII was expressed in tumour stroma most strikingly in blood vessels and capillaries, and in the muscle layer of the bowel wall.
  
  
  CONCLUSIONS
  Elevated endostatin levels in CRC correlate with systemic inflammation and invasion through the muscularis propria. Increased endostatin level may be a result of invasion-related cleavage of collagen XVIII expressed in the bowel wall. The negative correlations between serum endostatin and intratumoural mast cells and immature dendritic cells may reflect angiogenesis inhibition by endostatin.
authors.affiliation: 1] Department of Pathology, University of Oulu, POB 5000, 90014 Oulu, Finland [2] Oulu University Hospital, POB 21, 90029 Oulu, Finland [3] Medical Research Center Oulu, POB 21, 90029 Oulu, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Kantola
authors.affiliation: 1] Department of Pathology, University of Oulu, POB 5000, 90014 Oulu, Finland [2] Oulu University Hospital, POB 21, 90029 Oulu, Finland [3] Medical Research Center Oulu, POB 21, 90029 Oulu, Finland.
authors.forename: J P
authors.initials: JP
authors.lastname: Väyrynen
authors.affiliation: 1] Oulu University Hospital, POB 21, 90029 Oulu, Finland [2] Medical Research Center Oulu, POB 21, 90029 Oulu, Finland [3] Department of Surgery, University of Oulu, POB 5000, 90014 Oulu, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Klintrup
authors.affiliation: 1] Oulu University Hospital, POB 21, 90029 Oulu, Finland [2] Medical Research Center Oulu, POB 21, 90029 Oulu, Finland [3] Department of Surgery, University of Oulu, POB 5000, 90014 Oulu, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Mäkelä
authors.affiliation: Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, POB 5400, 90014 Oulu, Finland.
authors.forename: S M
authors.initials: SM
authors.lastname: Karppinen
authors.affiliation: Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, POB 5400, 90014 Oulu, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Pihlajaniemi
authors.affiliation: 1] Department of Pathology, University of Oulu, POB 5000, 90014 Oulu, Finland [2] Oulu University Hospital, POB 21, 90029 Oulu, Finland [3] Medical Research Center Oulu, POB 21, 90029 Oulu, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Autio-Harmainen
authors.affiliation: 1] Department of Pathology, University of Oulu, POB 5000, 90014 Oulu, Finland [2] Oulu University Hospital, POB 21, 90029 Oulu, Finland [3] Medical Research Center Oulu, POB 21, 90029 Oulu, Finland.
authors.forename: T J
authors.initials: TJ
authors.lastname: Karttunen
authors.affiliation: 1] Department of Pathology, University of Oulu, POB 5000, 90014 Oulu, Finland [2] Oulu University Hospital, POB 21, 90029 Oulu, Finland [3] Medical Research Center Oulu, POB 21, 90029 Oulu, Finland.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mäkinen
authors.affiliation: 1] Department of Pathology, University of Oulu, POB 5000, 90014 Oulu, Finland [2] Oulu University Hospital, POB 21, 90029 Oulu, Finland [3] Medical Research Center Oulu, POB 21, 90029 Oulu, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Tuomisto
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D043170:Collagen Type XVIII / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood* / Q000150:complications / Q000473:pathology; D043169:Endostatins / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness
chemical_list: D014408:Biomarkers, Tumor; D043170:Collagen Type XVIII; D043169:Endostatins