Apoptosis resistance of neuroendocrine phenotypes in prostatic adenocarcinoma

BACKGROUND. Neuroendocrine (NE) differentiation has been implicated in prostate cancer progression and hormone therapy failure. It has been shown that prostate cancer cells with NE features lack proliferation activity in vitro and in vivo. The current study reports on the apoptotic status of NE phenotypes in human prostate cancer. METHODS. Double-label techniques were used for simultaneous demonstration of the endocrine marker chromogranin A (ChrA) and DNA fragmentation assessed by the terminal transferase-mediated biotinylated 16-desoxy-uridine-tri-phosphate (bio-16-dUTP) nick-end-labeling (TUNEL) assay. The material included primary prostatic adenocarcinoma (n = 18), lymph node metastases (n = 5), bone metastases (n = 2), and recurrent lesions (n = 10) showing NE differentiation at the immunohistochemical level. RESULTS. Irrespective of grades, stages, and the degree of NE differentiation, DNA fragmentation was restricted to exocrine (ChrA-negative) tumor cells and was undetectable in most of NE tumor cells expressing ChrA. At least 0.16% of ChrA-positive tumor cells revealed DNA fragmentation assessed by the TUNEL assay. CONCLUSION. The present data suggest that the vast majority of prostate cancer cells with NE features escapes programmed cell death. This escape may contribute significantly to their drug resistance and their malignant potential. (C) 2002 Wiley-Liss, Inc.