Substrate gelatin zymogrophy analysis of matrix metalloproteinase-2 and -9 (gelatinase A and B) in sera from patients with benign and malignant prostate disease

Background: It is widely recognized that the serum prostate-specific antigen (PSA) levels as a biomarker of prostate cancer is imperfect, in that it can have many false positive elevations attributable to benign hyperplasia and subclinical prostatic inflammation. There are increasing data that support a positive correlation between gelatinases (MMP-2 and MMP-9) activity and tumor cell invasion and tumor aggressiveness. Objectives: We evaluate gelatinolytic activities in the sera of patients with prostate carcinoma (PCa) and benign prostate hyperplasia (BPH) in order to verify whether MMP-2 and MMP-9 might have potential as non invasive biomarkers. Methods: By gelatin zymography we verified MMP activity in a total of 42 patients. Of these 8 had benign prostate hyperplasia and 34 had carcinoma. A total of 16 normal healthy volunteers with no concomitant illness were used as control. Results: Four dominant proteinases were detected migrating at ~ 240, 130, 92 and 72 kDa. The most abundant lytic activity is at 92 kDa (MMP-9); whereas MMP-2 is present in lesser quantities. MMP-9 activity is significantly enhanced in the sera from patients with cancer compared with control individuals (p=0.003). Moreover, MMP-9/MMP-2 ratio was able to discriminate cancer patients from healthy subjects as well as from BPH, and the ROC curve showed that the ratio was a significant predictor of prostate cancer with sensitivity of 80% and specificity of 87%. Conclusions: These results suggest that the inexpensive measurement of MMPs in serum may serve as a suitable supplementary tool to distinguish between patients with prostate cancer and patients with BPH, and the addition of these enzymes to currently available PSA and/or f-PSA/t-PSA ratio might provide clinicians additional objective information on prostate carcinomas.