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Title:
Effects of Macrophage Migration Inhibitory Factor, Vascular Endothelial Growth Factor, CD34-Labeled Microvessel Density, and Inhibitor of Growth 4 on the Onset, Progression, and Angiogenesis of Prostate Cancer and Their Correlation
Authors:  Chaoqi Wang, M.D., and Shan Liang, M.M.
  Objective: To evaluate the effects of macrophage migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF), CD34-labeled microvessel density (MVD), and inhibitor of growth 4 (ING4) on the onset, progression, and angiogenesis of prostate cancer (PCa), and to study their correlation.
Study Design:
The tissue samples of 2 groups of patients whose ages were not statistically different were selected, including 43 PCa and 18 benign prostatic hy- perplasia (BPH) ones. The expressions of MIF, VEGF, and ING4 as well as MVD were detected by immunohistochemical staining. All stained sections were observed by 2 experienced pathologists using the double-blinded method. MVD was counted according to Weidner’s criteria.
Results:
The positive expression rates of MIF in BPH and PCa tissues were 16.67% and 83.72%, respectively (p<0.05), and those of VEGF increased to 33.33% and 86.04%, respectively (p<0.05). The MVD values of BPH and PCa tissues rose to 34.81±6.19 and 63.95±18.63, respectively (p<0.05). In the PCa group the positive expression rates of MIF and VEGF as well as MVD increased with rising Gleason score. The positive rates of MIF scored 2–6 points (55.56%), 7 points (81.82%), and 8–10 points (91.30%), respectively (p<0.05), and those of VEGF scored 2–6 points (66.67%), 7 points (81.82%), and 8–10 points (95.65%), respectively (p<0.05). The positive rates of ING4 scored 2–6 points (77.78%), 7 points (54.54%), and 8–10 points (21.37%), respectively. The MVD values scored 2–6 points (46.86±5.21), 7 points (55.12±7.01), and 8–10 points (80.96±10.11), respectively (p<0.05). MIF and VEGF expressions as well as MVD were elevated in PCa tissue with increasing clinical stage, but ING4 expression decreased (p<0.05). The expression rate of MIF was 66.67% at stage II, 88.89% at stage III, and 100.00% at stage IV, and that of VEGF was 73.33% at stage II, 83.33% at stage III, and 100.00% at stage IV (p<0.05). The expression rate of ING4 was 73.33% at stage II, 33.33% at stage III, and 10.00% at stage IV (p<0.001). MVD was 55.04±14.15 at stage II, 72.41±16.27 at stage III, and 79.87±12.73 at stage IV (p<0.05). In PCa tissue there was a positivecorrelation between MIF, VEGF expressions, and MVD (p<0.05). ING4 expression was negatively correlated with the other 3 (p<0.05).
Conclusion:
Decrease in ING4 expression and over-expression of MIF and VEGF in PCa tissue played an important role in angiogenesis and progression. Studying MIF, VEGF, MVD, and ING4 provides valuable evidence for the onset, progression, and prognosis prediction of PCa.
Keywords:  CD34, macrophage migration inhibitory factor, microvessel density, prostate, prostate cancer, vascular endothelial growth factor
   
   
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