Macrophage migration inhibitory factor evaluation compared with prostate specific antigen as a biomarker in patients with prostate carcinoma.
BACKGROUND
Cytokines are polypeptides that constitute a class of chemical mediator molecules that modulate cell growth by inducing specific target gene expression. The objective of this study was to evaluate the clinical usefulness of serum evaluation of the cytokine macrophage migration inhibitory factor (MIF) in patients undergoing routine prostate specific antigen (PSA) screening.


METHODS
In this preliminary, retrospective study, the authors report the development of an enzyme-linked immunosorbent assay (ELISA) for MIF determination in serum samples. A polymerase chain reaction (PCR)-based assay investigated associations between MIF expression and prostate carcinoma (CaP). The authors developed a relative quantitative reverse transcriptase-PCR assay to determine MIF mRNA amounts within laser-capture microscopy (LCM)-dissected prostate epithelial cells.


RESULTS
A comparison of serum MIF levels and total PSA levels identified a positive correlation (correlation coefficient [r2] = 0.61; P < 0.001; n = 509 patients), suggesting an association between elevated serum concentrations of these proteins and CaP. A correlation of serum MIF levels with a diagnosis of CaP demonstrated that patients with a previous CaP diagnosis had significantly elevated serum MIF concentrations (mean +/- standard deviation, 6.8 +/- 0.87 ng/mL; P < 0.001). To associate altered serum MIF levels with MIF mRNA expression within prostate epithelial cells, LCM-dissected prostate epithelial cells (formalin fixed biopsies from three different patients) were used to determine MIF mRNA amounts by PCR analysis. On average, MIF mRNA amounts were 6.5 times higher in CaP epithelial cells that were invasive to the margin compared with MIF mRNA amounts in normal prostate epithelial cells within the same biopsy specimen.


CONCLUSIONS
The ELISA data from the current study suggested an association between increased MIF expression and CaP and suggested that serum MIF concentration may serve as a prognostic marker for CaP.
Meyer-Siegler
Katherine L
KL
Research and Development, Bay Pines Veterans Administration Medical Center, Bay Pines, Florida 33744, USA. ksiegler@hsc.usf.edu
Bellino
Michael A
MA
Tannenbaum
Myron
M
D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen