The majority of prostate cancers show some degree of neuroendocrine differentiation. It was previously demonstrated that chromogranin A, a constituent of large dense core vesicles of neuroendocrine cells, is frequently elevated in patients with metastatic prostate cancer. We evaluate the expression of secretoneurin, which is generated by proteolytic processing of secretogranin II (chromogranin C), in patients with prostate disease.

Materials and Methods:

Secretoneurin was measured in sera of 16 healthy men whose blood was drawn for prostate cancer screening (controls), and in 9 patients with prostatitis, 19 with benign prostate hyperplasia and 54 with prostate cancer detected by radioimmunoassay. Therapy resistant disease (clinical stage D3) was noted in 20 prostate cancer cases. Serum prostate specific antigen was measured in all patients and controls. In addition, chromogranin A, prostate acid phosphatase and interleukin-6 were determined in patients with D3 prostate cancer. Molecular properties of secretoneurin immunoreactivity were analyzed by gel filtration chromatography followed by radioimmunoassay.


Mean secretoneurin was 58.9 ± 8 fmol./ml. in patients with therapy resistant prostate cancer. Levels were significantly higher than those measured in sera from controls and patients with prostatitis, benign prostatic hyperplasia and pT2 or pT3 prostate cancer. There was a statistically significant correlation between secretoneurin and chromogranin A in patients with endocrine therapy failure (r = 0.543, p <0.05). There was no correlation between serum secretoneurin and prostate specific antigen, prostate acid phosphatase or interleukin-6. Gel filtration chromatography analysis of sera of 3 patients with D3 prostate cancer revealed a peak of secretoneurin immunoreactivity where intact secretoneurin elutes, thus showing that the processed peptide is circulating in the blood.


Secretoneurin is elevated in sera of patients with endocrine therapy refractory prostate cancer. Our results support the concept that neuroendocrine differentiation is associated with prostate cancer progression.


  • 1 : Secretogranin II: molecular properties, regulation of biosynthesis and processing to the neuropeptide secretoneurin. Prog Neurobiol1995; 46: 49. Google Scholar
  • 2 : Presence of chromogranins and regulation of their synthesis and processing in a neuroendocrine prostate tumor cell line. Prostate1998; 8: 80. Google Scholar
  • 3 : Neuroendocrine differentiation in prostatic carcinoma: an update. Prostate1998; 8: 74. Google Scholar
  • 4 : Do neuroendocrine cells in human prostate cancer express androgen receptor?. Histochemistry1993; 100: 393. Google Scholar
  • 5 : Elevated plasma chromogranin-A concentrations in prostatic carcinoma. J Urol1991; 146: 358. LinkGoogle Scholar
  • 6 : Plasma neuroendocrine markers in patients with benign prostatic hyperplasia and prostatic carcinoma. J Urol1996; 155: 1340. LinkGoogle Scholar
  • 7 : Immunoassay and immunohistology studies of chromogranin A as a neuroendocrine marker in patients with carcinoma of the prostate. Urology1996; 48: 58. Google Scholar
  • 8 : Neuroendocrine differentiation in carcinomas of the prostate: do neuroendocrine serum markers reflect immunohistochemical findings?. Prostate1997; 30: 1. Google Scholar
  • 9 : Plasma chromogranin A in prostatic carcinoma and neuroendocrine tumors. J Urol1997; 157: 565. LinkGoogle Scholar
  • 10 : Serum chromogranin A: early detection of hormonal resistance in prostate cancer patients. J Clin Lab Anal1998; 12: 20. Google Scholar
  • 11 : Investigation on serum neuron-specific enolase in prostatic cancer diagnosis and monitoring: comparative study of a multiple tumor marker assay. Prostate1991; 19: 23. Google Scholar
  • 12 : Secretogranin II: relative amounts and processing to secretoneurin in various rat tissues. J Neurochem1996; 66: 1312. Google Scholar
  • 13 : Secretoneurin—a neuropeptide generated in brain, adrenal medulla and other endocrine tissues by proteolytic processing of secretogranin II (chromogranin C). Neuroscience1993; 53: 359. Google Scholar
  • 14 : Levels and molecular properties of secretoneurin-immunoreactivity in the serum and urine of control and neuroendocrine tumor patients. J Clin Endocrinol Metab2000; 85: 355. Google Scholar
  • 15 : Interleukin-6: a candidate mediator of human prostate cancer morbidity. Urology1995; 45: 542. Google Scholar
  • 16 : Clinical significance of elevation in neuroendocrine factors and interleukin-6 in metastatic prostate cancer. Urol Oncol1995; 1: 246. Google Scholar
  • 17 : Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer. Proc Natl Acad Sci USA1994; 91: 4673. Google Scholar
  • 18 : Neuroendocrine differentiation in human prostatic tumor models. Am J Pathol1996; 149: 859. Google Scholar
  • 19 : Kinetics of neuroendocrine differentiation in an androgen-dependent human prostate xenograft model. Am J Pathol1999; 154: 543. Google Scholar
  • 20 : Chromogranin A and B and secretogranin II in prostatic adenocarcinomas: neuroendocrine expression in patients untreated and treated with androgen deprivation therapy. Prostate1998; 34: 113. Google Scholar
  • 21 : Specific binding of a 125I-secretoneurin analogue to a human monocytic cell line. J Neuroimmunol1998; 86: 87. Google Scholar
  • 22 : Calcitonin stimulates growth of human prostate cancer cells through receptor-mediated increase in cyclic adenosine 3′,5′-monophosphates and cytoplasmid Ca2+ transients. Endocrinology1994; 134: 596. Google Scholar
  • 23 : Vasoactive intestinal peptide stimulates prostate-specific antigen secretion by LNCaP prostate cancer cells. Regul Pept1996; 65: 153. Google Scholar

From the Departments of Pharmacology, Urology, Internal Medicine, and Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria