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. |
