title: Measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improves prostate cancer diagnosis.
abstract: OBJECTIVE
  Current serum testing for the detection of prostate cancer (PCa) lacks specificity. On diagnosis, the optimal therapeutic pathway is not clear and tools for adequate risk assessment of localized PCa progression are not available. This leads to a significant number of men having unnecessary diagnostic biopsies and surgery. A search for novel tumor markers identified macrophage inhibitory cytokine 1 (MIC-1) as a potentially useful marker. Follow-up studies revealed MIC-1 overexpression in local and metastatic PCa whereas peritumoral interstitial staining for MIC-1 identified lower-grade tumors destined for recurrence. Consequently, we sought to assess serum MIC-1 measurement as a diagnostic tool.
  
  
  METHODS
  Using immunoassay determination of serum MIC-1 concentration in 1,000 men, 538 of whom had PCa, we defined the relationship of MIC-1 to disease variables. A diagnostic algorithm (MIC-PSA score) based on serum levels of MIC-1, total serum prostate-specific antigen, and percentage of free prostate-specific antigen was developed.
  
  
  RESULTS
  Serum MIC-1 was found to be an independent predictor of the presence of PCa and tumors with a Gleason sum > or =7. We validated the MIC-PSA score in a separate population and showed an improved specificity for diagnostic blood testing for PCa over percentage of free prostate-specific antigen, potentially reducing unnecessary biopsies by 27%.
  
  
  CONCLUSIONS
  Serum MIC-1 is an independent marker of the presence of PCa and tumors with a Gleason sum of > or =7. The use of serum MIC-1 significantly increases diagnostic specificity and may be a future tool in the management of PCa.
authors.affiliation: Centre for Immunology at St. Vincent's Hospital, Sydney, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Ward
authors.forename: Mathew
authors.initials: M
authors.lastname: Law
authors.forename: Mark
authors.initials: M
authors.lastname: Hunter
authors.forename: Asne R
authors.initials: AR
authors.lastname: Bauskin
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Garret M
authors.initials: GM
authors.lastname: Hampton
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Russell
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D055436:Growth Differentiation Factor 15; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D017430:Prostate-Specific Antigen