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 metal loproteinases 2 and 3 (MMP-2, MMP-3). These enzymes, also known as typ e IV collagenase and stromelysin-1, respectively, are thought to contr ibute to cancer invasion and metastasis and so represent potential pro gnostic markers and therapeutic targets. Immunhistochemistry was used to study expression of TGF beta 1, MMP-2, and MMP-3 in 37 cases of pro static hyperplasia and adenocarcinoma of varying grades and stages. Cy toplasmic TGF beta 1 was weakly expressed in normal secretory epitheli al cells and moderately to strongly expressed in basal and stromal cel ls, with more intense stromal staining in hyperplastic glands. TGF bet a 1 staining in adenocarcinomas ranged from weak to strong, whereas hi gh-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 aden ocarcinomas and accompanying PIN. MMP-2 staining ranged from weak to s trong in carcinoma and PIN, was weak in normal secretory cells, and wa s 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 path ogenesis of prostatic hyperplasia and cancer invasion, these results d o not support a role for their use as immunohistochemical prognostic m arkers.