TY - JOUR
T1 - Recurrence-free survival in prostate cancer is related to increased stromal TRAIL expression
AU - Anees, Mariam
AU - Horak, Peter
AU - El-Gazzar, Ahmed
AU - Susani, Martin
AU - Heinze, Georg
AU - Perco, Paul
AU - Loda, Massimo
AU - Lis, Rosina
AU - Krainer, Michael
AU - Oh, William K.
PY - 2011/3/15
Y1 - 2011/3/15
N2 - BACKGROUND: TRAIL (tumor necrosis factor related apoptosis-inducing ligand) is involved in tumor immune surveillance and, thus, may be a potential cancer therapy. TRAIL expression in the tumor microenvironment has been shown to impact cancer survival in multiple tumor types, including ovarian cancer. We studied TRAIL expression and outcomes in patients with prostate cancer. METHODS: A tissue microarray (TMA) of 200 prostate cancer patients and benign prostate tissue controls was used to assess the epithelial and stromal protein expression of TRAIL, death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and the FLICE inhibitory protein (FLIPL). We correlated these expression patterns with clinicopathological parameters and determined its impact on recurrence-free survival. RESULTS: Nearly all (99.5%) prostate cancer tissues examined displayed either decreased expression of pro-apoptotic TRAIL receptors, increased FLIPL expression, or both. We observed elevated death receptor, decoy receptor, FLIPL, and epithelial TRAIL expression in prostate cancer epithelium. TRAIL expression in the stromal tumor microenvironment surrounding the prostate cancer was markedly lower. Elevated TRAIL expression in the tumor microenvironment was also significantly associated with increased recurrence-free survival (P =.014), after controlling for other prognostic markers. In contrast, epithelial expression of TRAIL did not have an effect on overall survival. CONCLUSIONS: Expression of the components of the pro-apoptotic TRAIL pathway is altered in prostate cancer.
AB - BACKGROUND: TRAIL (tumor necrosis factor related apoptosis-inducing ligand) is involved in tumor immune surveillance and, thus, may be a potential cancer therapy. TRAIL expression in the tumor microenvironment has been shown to impact cancer survival in multiple tumor types, including ovarian cancer. We studied TRAIL expression and outcomes in patients with prostate cancer. METHODS: A tissue microarray (TMA) of 200 prostate cancer patients and benign prostate tissue controls was used to assess the epithelial and stromal protein expression of TRAIL, death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and the FLICE inhibitory protein (FLIPL). We correlated these expression patterns with clinicopathological parameters and determined its impact on recurrence-free survival. RESULTS: Nearly all (99.5%) prostate cancer tissues examined displayed either decreased expression of pro-apoptotic TRAIL receptors, increased FLIPL expression, or both. We observed elevated death receptor, decoy receptor, FLIPL, and epithelial TRAIL expression in prostate cancer epithelium. TRAIL expression in the stromal tumor microenvironment surrounding the prostate cancer was markedly lower. Elevated TRAIL expression in the tumor microenvironment was also significantly associated with increased recurrence-free survival (P =.014), after controlling for other prognostic markers. In contrast, epithelial expression of TRAIL did not have an effect on overall survival. CONCLUSIONS: Expression of the components of the pro-apoptotic TRAIL pathway is altered in prostate cancer.
KW - Prostate cancer
KW - death receptors
KW - recurrence-free survival
KW - tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
UR - https://www.scopus.com/pages/publications/79952408952
U2 - 10.1002/cncr.25504
DO - 10.1002/cncr.25504
M3 - Article
C2 - 21381010
AN - SCOPUS:79952408952
SN - 0008-543X
VL - 117
SP - 1172
EP - 1182
JO - Cancer
JF - Cancer
IS - 6
ER -