Integrin-linked kinase expression increases with prostate tumor grade

Purpose: Integrin-linked kinase (ILK) overexpression can suppress anoikis, promote anchorage-independent cell cycle progression, and induce tumorigene sis and invasion. Inhibition of ILK in prostatic adenocarcinoma (CaP) cells elicits cell cycle arrest and induces apoptosis, Furthermore, ILK expressi on increases with androgen-independent progression of human CaP cell lines, suggesting that increased ILK expression may be associated with CaP progre ssion. Experimental Design: To assess whether ILK expression may be related to CaP development and/or progression, we have evaluated ILK expression by immuno histochemistry in 100 human prostate tissues. Results: We show that ILK expression increases significantly with Cap progr ession. ILK immunostaining is specifically increased in high-grade, primary human Cap relative to adjacent benign prostatic hyperplasia (P < 0,001), b enign prostatic hyperplasia from patients without cancer (P < 0.002), and l ow-grade CaP (P = 0.003), ILK overexpression is specifically associated wit h the increased proliferative index (P = 0.001) that typifies CaP progressi on, Strikingly, intense uniform ILK immunostaining was inversely related to 5-year patient survival (P = 0.004). Conclusions: ILK expression increases dramatically with CaP progression. IL K expression is also specifically related to the disproportionately increas ed proliferative index that contributes to the net gain of CaP cells during progression. Finally, enhanced ILK expression is inversely related to 5-ye ar patient survival. These data therefore implicate increased ILK expressio n in prostate tumor progression.