Transforming growth factor-beta 1 and matrix metalloproteinases in prostatic adenocarcinoma and hyperplasia - Coordinated patterns of immunohistochemical expression

In vitro studies have suggested that transforming growth factor-beta 1 (TGF beta 1) may coordinately regulate the expression of matrix metalloproteinases 2 and 3 (MMP-2, MMP-3). These enzymes, also known as type IV collagenase and stromelysin-1, respectively, are thought to contribute to cancer invasion and metastasis and so represent potential prognostic markers and therapeutic targets. Immunhistochemistry was used to study expression of TGF beta 1, MMP-2, and MMP-3 in 37 cases of prostatic hyperplasia and adenocarcinoma of varying grades and stages. Cytoplasmic TGF beta 1 was weakly expressed in normal secretory epithelial cells and moderately to strongly expressed in basal and stromal cells, with more intense stromal staining in hyperplastic glands. TGF beta 1 staining in adenocarcinomas ranged from weak to strong, whereas high-grade prostatic intraepithelial neoplasia (PIN) was more uniformly strongly positive. MMP-3 was not detected in nonneoplastic tissues but showed at least low to moderate levels of expression in 24 of 29 adenocarcinomas and accompanying PIN. MMP-2 staining ranged from weak to strong in carcinoma and PIN, was weak in normal secretory cells, and was moderate in basal cells and hyperplastic secretory cells. Regression analysis demonstrated a significant positive correlation between MMP-3 and TGF beta 1 levels and a weak correlation between MMP-2 and tumor grade. No correlation was found between stage and any of the markers nor between MMP-2 and MMP-3 to indicate in vivo coordinated regulation of these two MMPs. Although these proteins may contribute to the pathogenesis of prostatic hyperplasia and cancer invasion, these results do not support a role for their use as immunohistochemical prognostic markers.