Matrix metalloproteinase 9 is associated with Gleason score in prostate cancer but not with prognosis

Abstract

Prostate cancer is the most common cancer in North American men. Among men diagnosed with prostate cancer in more than three cores or with high grade prostate cancer, many experience long disease-free survival. However, these patients still undergo radical treatment while they could benefit from active surveillance with complementary therapy. Matrix metalloproteinase 9 degrades type IV collagen and activates tumorigenic factors and is thus a potential prognostic factor and therapeutic target. This study was thus aimed at investigating the role of matrix metalloproteinase 9 on prostate cancer progression. We correlated matrix metalloproteinase 9 immunohistochemical expression by cancer, stromal and benign epithelial cells with prostate cancer disease-free survival among a cohort composed of 187 pT3NxM0 prostate cancer patients. Median follow-up was 4.63 years and a recurrence occurred in 67 men (35.3%). Matrix metalloproteinase 9 immunostaining was cytoplasmic and expressed at different levels in cancer (94.1%), stromal (87.7%) and benign epithelial cells (94.1%). High levels (>50% of cells) of matrix metalloproteinase 9 expression by prostate cancer cells was strongly associated with high Gleason score (P = .0009). In stromal cells and in benign epithelial cells, high matrix metalloproteinase 9 expression levels were respectively associated with low pT3 substage (P = .046) and with low initial serum prostate-specific antigen levels (P = .006). Matrix metalloproteinase 9 expression level by any cell type was not associated with prostate cancer disease-free survival. These results show that matrix metalloproteinase 9 is overexpressed by cancer cells in high grade tumors and by stromal and benign epithelial cells in lower substage tumors.