Neuroendocrine differentiation in prostate cancer: is it detectable and treatable?



We were interested in the article by Sciarra et al. [1] suggesting that neuroendocrine markers might complement the PSA assay in selected cases of poorly differentiated tumours, and that an increase in chromogranin A expression, despite low PSA levels, may indicate progression and a poor prognosis. Tissue neuroendocrine markers including chromogranin A and neurone-specific enolase have been identified in all 18 patients with clinically progressive androgen-independent prostate cancer and low serum PSA levels [2], leading to the belief that most low serum-PSA metastatic prostate cancers were neuroendocrine in origin. Our current work with treatment-naive patients with metastatic prostate cancer and low serum PSA levels at presentation has shown no additional benefit from neuroendocrine markers. Tissue chromogranin A immunostaining was negative in 22 of 33 cases (66%), six of whom were also tissue PSA-negative. In five cases (15%) there was a 2+ intensity of immunostaining, but the pattern of staining was very focal. In the one case where there was 3+ intensity of chromogranin A immunostaining this was seen in very occasional cells, and not sufficient to describe the tumour as neuroendocrine [3]. CD56, which has also been useful in detecting neuroendocrine differentiation [4], was unhelpful, being focally positive in three of 33 (9%) cases only. Our experience suggests that neuroendocrine markers are of no additional benefit in most metastatic prostate cancers presenting with low serum PSA levels.