Neuroendocrine cells in human prostate over-express the anti-apoptosis protein survivin

BACKGROUND. Neuroendocrine (NE) differentiation may be related to the growt h and progression of prostate cancer, especially androgen-insensitive tumor s. Recently the overexpression of a new anti-apoptosis protein, survivin, h as attracted attention for its potential implication in many human cancers. The fact that NE cells in prostate are bcl-2 negative prompted us to inves tigate if the prostatic NE cells over-express survivin. MATERIALS AND METHODS. Double immunohistochemical staining and immunofluore scence of chromogranin A (CgA) and survivin were performed in 57 patients w ith localized prostate cancer who underwent radical prostatectomy. The term inal deoxynucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end- labeling (TUNEL) method was used for apoptosis detection in three prostate cancer specimens with NE differentiation. The relationship between NE diffe rentiation and clinicopathological characteristics, disease progression as well as patient survival, were analyzed retrospectively. RESULTS. It was found that NE cells in both benign and malignant prostate t issues overexpressed the anti-apoptosis protein survivin. While apoptosis w as detected in non-NE epithelial cells, all NE cells were negative for apop tosis detection. During the period of followup, 17 (63%) of 27 patients wit h NE differentiation had prostate cancer progression, while 12 (40%) of 30 patients without NE differentiation had systemic prostate cancer progressio n. 10 (37%) of 27 patients with NE differentiation died from prostate cance r during the period of follow up, while 6 (20%) of 30 patients without NE d ifferentiation died from prostate cancer. However, none of these characteri stics reached statistical significance, probably because of the small numbe r of cases enrolled. CONCLUSIONS. This study discovers that all the prostatic NE cells express t he new anti-apoptosis protein survivin. This provides a strong molecular ba sis for the hypothesis that NE cells may endure stressful conditions and es cape from apoptosis. While our results suggest a trend of NE differentiatio n with poorer prognosis, the prognosis implication cannot be concluded due to our small sample size. Prostate 48:7-15, 2001. (C) 2001 Wiley-Liss, Inc.