Elevated levels of serum secretoneurin in patients with therapy resistant carcinoma of the prostate

Purpose: The majority of prostate cancers show some degree of neuroendocrin e differentiation. It was previously demonstrated that chromogranin A, a co nstituent of large dense core vesicles of neuroendocrine cells, is frequent ly elevated in patients with metastatic prostate cancer. We evaluate the ex pression 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 p atients with prostatitis, 19 with benign prostate hyperplasia and 54 with p rostate cancer detected by radioimmunoassay. Therapy resistant disease (cli nical stage D3) was noted in 20 prostate cancer cases. Serum prostate speci fic antigen was measured in all patients and controls. In addition, chromog ranin A, prostate acid phosphatase and interleukin-6 were determined in pat ients with D3 prostate cancer. Molecular properties of secretoneurin immuno reactivity were analyzed by gel filtration chromatography followed by radio immunoassay. Results: Mean secretoneurin was 58.9 +/- 8 fmol./ml. in patients with thera py resistant prostate cancer. Levels were significantly higher than those m easured in sera from controls and patients with prostatitis, benign prostat ic hyperplasia and pT2 or pT3 prostate cancer. There was a statistically si gnificant correlation between secretoneurin and chromogranin A in patients with endocrine therapy failure (r = 0.543, p <0.05). There was no correlati on between serum secretoneurin and prostate specific antigen, prostate acid phosphatase or interleukin-6. Gel filtration chromatography analysis of se ra of 3 patients with D3 prostate cancer revealed a peak of secretoneurin i mmunoreactivity where intact secretoneurin elutes, thus showing that the pr ocessed peptide is circulating in the blood. Conclusions: Secretoneurin is elevated in sera of patients with endocrine t herapy refractory prostate cancer. Our results support the concept that neu roendocrine differentiation is associated with prostate cancer progression.