Undifferentiated carcinoma of the prostate with small cell features: immunohistochemical subtyping and reflections on histogenesis.

To investigate the histogenesis of undifferentiated carcinoma of the prostate with small cell features we analysed the expression of neuroendocrine (NE) markers, the androgen receptor (AR), and prostate-specific antigen (PSA) in 19 undifferentiated carcinomas of the prostate. The proliferative activity (MIB-1/Ki67) of the tumours was examined, and the clinical data reviewed. The results identified two groups: carcinomas in group 1 were positive for PSA and AR and negative for NE markers. The mean MIB-1 labelling index (LI) was 34.8% and the mean serum PSA value 56.4 ng/ml. Two of the 7 patients died within 12 months after tumour diagnosis. The tumours in group 2 were NE differentiated small cell carcinomas (SCC), which were negative for PSA and AR. The mean MIB-1 LI was 82.6% and the mean serum PSA value 7.1 ng/ml. Seven of the 10 patients died between 2 and 12 months after tumour diagnosis. Positive staining for NE markers in combination with negative staining for PSA and AR and a high MIB-1 LI substantiated the diagnosis of a NE-SCC. We suggest that this tumour has a stem cell origin and does not derive from a dedifferentiated adenocarcinoma or from benign NE cells of the prostatic epithelium. This clear distinction of NE-SCC from NE-negative undifferentiated carcinoma is in accordance with the differing biological behaviour and response to therapy of the two tumour entities.