Measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improves prostate cancer diagnosis.
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.
Brown
David A
DA
Centre for Immunology at St. Vincent's Hospital, Sydney, Australia.
Stephan
Carsten
C
Ward
Robyn L
RL
Law
Mathew
M
Hunter
Mark
M
Bauskin
Asne R
AR
Amin
Janaki
J
Jung
Klaus
K
Diamandis
Eleftherios P
EP
Hampton
Garret M
GM
Russell
Pamela J
PJ
Giles
Graham G
GG
Breit
Samuel N
SN
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
D014408:Biomarkers, Tumor; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D017430:Prostate-Specific Antigen