Prognostic Significance of Gelatinases (A & B) and Angiogenesis in Prostatic Cancer: A Double Immunostaining Study
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Background: Gelatenases A&B (MMP-2 & -9) have been reported to be associated with tumor progression in various types of cancer, and several studies have reported their prognostic significance in prostatic cancer. They also play a key role in normal and pathological angiogenesis by mediating extracellular matrix degradation and/or controlling the biological activity of growth factors, chemokines and/or cytokines. Objectives: We studied the expression of MMP-2 & -9 in 53 radical prostatectomy specimens together with 17 benign nodular hyperplasia (BNH), in an attempt to elucidate their role in prostatic cancer (PC) progression and patient's outcome. Moreover, we studied simultaneously, CD34 expression in the same specimens to find out the role of MMP-2 & 9 in the promotion or inhibition of angiogenesis, a prerequisite for growth of malignant neoplasms. Material and Methods: lmmunohistochemical staining for MMP-2, MMP-9 and CD34 has been performed on formalin- fixed, paraffin-embedded material of 70 specimens (53 prostatic cancer and 13 benign nodular hyperplasia). Both the standard peroxidase/DAB and the APAAP/BCIP/NBT staining techniques and chromogens were used. Expression of markers studied was correlated statistically to patient's age, Gleason sum Score (GS), pathologic stage, safety margin invasion, local recurrence, bone metastases, and patient's outcome. Results: MMP-2 and MMP-9 were expressed in PC in 33/53 (62%) and 40/53 (75.1%) of cases respectively. Both markers were positivity correlated (p=0.01) with each other. A statistically significant correlation could be found between both MMP-2 & -9 expression and high GS (p=0.01 &p=0.004), pathological stage (p=0.01 & 0.01), and poor survival (p=0.002 and p=0.012, respectively). MMP-2 was correlated with local recurrence (p=0.02). High microvessel count (MVC) > 75 correlated positively with expression of both MMP-2 (pr-0.002) and MMP-9 (p=0.001). This was also visualized in situ, where areas with strong staining for both MMPs had a higher MVC. A high MVC >75 correlated with high GS (p=0.01), presence of bone metastases (0.02), high pathological stage (p=0.003) and poor survival (p=0.001). Conclusion: Both gelatinases A&B (MMP-2 & -9) are expressed in PC in > 50 of cases, and their presence in PC correlated with a high GS and pathological stage. MMP-2 had an impact on local recurrence, while presence of both markers indicated poor survival. Both MMPs promoted angiogenesis as shown by double immunostaining and by statistical results. MVC > 75 could be used as a prognostic indicator for poor survival (p=0.001) in PC.