title: Assessment of the biological variation of plasma tissue inhibitor of metalloproteinases-1.
abstract: BACKGROUND
  Tissue inhibitor of metalloproteinases-1 (TIMP-1) measurements in plasma may be useful for the early detection and prognosis of colorectal cancer (CRC). Data on analytical performance and normal intra- and interindividual biological variation are required in order to interpret the utility of TIMP-1 in CRC. The aim of this study was to establish the biological and analytical variation of plasma TIMP-1 in volunteers.
  
  
  METHODS
  Three separate studies were undertaken. 1: Plasma was collected from 23 volunteers 6 times within a 3-week period, first in September 2004 (round [R] 1), then repeated in May 2005 (R2) and May 2006 (R3) in the same group of individuals. TIMP-1 levels were determined by the MAC15 ELISA assay and with the Abbott ARCHITECT i2000 Immunoanalyzer. 2: Circadian variation was evaluated in plasma collected 7 times within a 24-hour period (n=16). 3: Effects of physical exercise were evaluated in plasma collected before and after bicycling (n=14). In studies 2 and 3 TIMP-1 levels were determined with the MAC15 ELISA assay only.
  
  
  RESULTS
  A significant correlation between TIMP-1 MAC15 and ARCHITECT i2000 was shown (rs=0.78, p<0.002), with consistently higher levels being detected by the ARCHITECT i2000. Median levels of TIMP-1 (ARCHITECT) at 8 a.m. in each round were 74.9 ng/mL (range 65.7-89.9) (R1), 87.3 ng/mL (range 72.7-127.9) (R2), and 81.9 ng/mL (range 66.8-113.6) (R3). The within-subject variation was 10.7%, the variation between rounds was 7.4%, and the intraclass correlation was 46.2%. Comparison between the 3 rounds and time of collection showed that TIMP-1 values decreased by 11% after storage for more than 16 months (p=0.0002). A systematic circadian variation in plasma TIMP-1 levels was not observed (p=0.17). No significant variation of plasma TIMP-1 was found in relation to physical exercise (p=0.92 [global test]).
  
  
  CONCLUSIONS
  Levels of plasma TIMP-1 in volunteers show limited circadian, day-to-day, week-to-week and season-to-season variation. In addition, physical exercise has no impact on plasma TIMP-1 levels. Possible storage-dependent decreases in plasma TIMP-1 levels warrant further investigation.
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre - Denmark. frederiksen@dadlnet.dk
authors.forename: C B
authors.initials: CB
authors.lastname: Frederiksen
authors.forename: A F
authors.initials: AF
authors.lastname: Lomholt
authors.forename: T
authors.initials: T
authors.lastname: Lottenburger
authors.forename: G J
authors.initials: GJ
authors.lastname: Davis
authors.forename: B L
authors.initials: BL
authors.lastname: Dowell
authors.forename: M A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: I J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: N
authors.initials: N
authors.lastname: Brunner
authors.forename: H J
authors.initials: HJ
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood; D001774:Blood Chemical Analysis; D002940:Circadian Rhythm; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D015444:Exercise; D005260:Female; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D019715:Tissue Inhibitor of Metalloproteinase-1