Immunohistochemical study of Fas, Fas ligand and interleukin‐1β converting enzyme expression in human prostatic cancer

Abstract

Objective To determine the cellular expression of Fas, Fas ligand and interleukin‐1β converting enzyme (ICE) in prostatic cancer. Patients and methods Specimens of prostate were obtained from 21 patients (mean age 66 years, sd 5) undergoing radical prostatectomy for prostatic cancer. Nine of the 21 patients had received endocrine therapy before surgery. Specimens were also obtained from 10 patients with benign prostatic hypertrophy (BPH) and during autopsy from 10 patients who had died from hormone‐unresponsive prostate cancer. Paraffin‐embedded sections were cut from the specimens and stained immunohistochemically to detect Fas, Fas ligand and ICE. Results Fas was expressed in all 21 of the cancer specimens while Fas ligand was detected in none and ICE was expressed in 11. The difference between the expression of Fas and ICE was significant (P<0.001). ICE was expressed in nine of 12 patients who were untreated before surgery and in two of nine treated with endocrine therapy (P<0.05). Fas expression was detected in the specimens from all 10 patients with BPH and in all 10 autopsy specimens; the expression tended to be more marked than that in specimens from total prostatectomy (P<0.1). Conclusion The expression of ICE was weaker than that of Fas in the total prostatectomy specimens, suggesting a possible interruption of the apoptotic signalling pathway. Prostates with BPH and hormone‐unresponsive cancer therefore showed no appreciable change in Fas expression when compared with total prostatectomy samples.

Role of inflammasomes and their regulators in prostate cancer initiation, progression and metastasis

“…These results suggest that caspase-1 downregulation is involved in prostate cancer cell survival. However, it has also been observed that stimulation of prostate cancer cells with dihydrotestosterone induces caspase-1 [19], and that treatment of prostate cancer cells with anti-androgens suppresses caspase-1 [20]. Given that androgen deprivation is involved in the regression or growth inhibition of early stage prostate cancers, it is plausible that the presence of androgens might promote aggressive forms of prostate cancer by inducing higher caspase-1 levels to propagate inflammation.…”

FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor β1–Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells

“…Elevated levels of FLIP can displace caspase-8 from the activated DR complex, acting as a dominant inhibitor of caspase-8 and thereby preventing the activation of distal caspases and cell death (15). Surgical specimens from normal human prostate, as well as both androgen responsive and unresponsive tumors, express Fas and FasL (16,17). TRAIL induces the apoptosis of both normal prostate epithelial cells (18) and prostate cancer cell lines (19,20).…”

Fas-mediated killing of primary prostate cancer cells is increased by mitoxantrone and docetaxel

“…Immunohistochemical studies of primary human prostate cancer tissues have shown expression of key apoptotic pathway proteins, including Fas and caspases (12,13). On the other hand, abundant expression of inhibitors of apoptosis, such as survivin and cellular inhibitors of apoptosis protein 1 and 2 (cIAP1 and cIAP2, respectively), have also been documented (14,15).…”

“…Without functional studies, it is not known whether the Fas pathway is operational in primary malignant prostate cells. In fact, based on expression profiling of such apoptotic mediators, it has been predicted that apoptotic signaling may be dramatically interrupted in prostate cancer tissues (12). To date, no functional studies have been conducted looking at Fas-mediated killing of patient-derived primary prostate tumor cells.…”