Immunohistochemical analysis of neuroendocrine differentiation in prostate cancer.

OBJECTIVE To clarify the significance of neuroendocrine differentiation in prostate cancer. METHODS We immunohistochemically examined 96 samples of prostatic cancers obtained from radical prostatectomies using a specific neuroendocrine marker and various neuropeptides, as well as markers for cell proliferation, angiogenesis and androgen-receptor expression. RESULTS We frequently found neuroendocrine cells in atrophic glands with or without chronic inflammation in nontumorous tissues. Neuroendocrine cells were detected in 36.5% of prostate cancer samples overall, but had no significant correlation to angiogenesis, cell proliferation or biochemical recurrence. However, patients with a high frequency of neuroendocrine cells (9.4%) tended to undergo preoperative hormonal therapy (p = 0.060), which led to their cancers being atrophic with inflammation. The neuroendocrine cells in these patients contained calcitonin-positive cells (p <or= 0.0001), and calcitonin positivity showed significant association with high Gleason score (p = 0.045) in the group without preoperative therapy. In the group undergoing preoperative therapy, a high prostate-specific antigen titer at first admission correlated to significant biochemical recurrence (p = 0.003). CONCLUSIONS Neuroendocrine cells may be induced under conditions of atrophy with or without chronic inflammation in both noncancerous glands and in cancers, including calcitonin-positive cells. Neither positive neuroendocrine nor positive androgen-receptor status appears predictive for biochemical recurrence.