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

To investigate the histogenesis of undifferentiated carcinoma of the prosta te with small cell features we analysed the expression of neuroendocrine (N E) markers, the androgen receptor (AR), and prostatic-specific antigen (PSA ) in 19 undifferentiated carcinomas of the prostate. The proliferative acti vity (MIB-1/Ki67) of the tumours was examined, and the clinical data review ed. The results identified two groups: carcinomas in group I 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 patien ts died within 12 months after tumour diagnosis. The tumours in group 2 wer e NE differentiated small cell carcinomas (SCC), which were negative for PS A and AR. The mean MIB-1 LI was 82.6% and the mean serum PSA value 7.1 ng/m l. Seven of the 10 patients died between 2 and 12 months after tumour diagn osis. Positive staining for NE markers in combination with negative stainin g for PSA and AR and a high MIB-1 LI substantiated the diagnosis of a NE-SC C. We suggest that this tumour has a stem cell origin and does not derive f rom a dedifferentiated adenocarcinoma or from benign NE cells of the prosta tic epithelium. This clear distinction of NE-SCC from NE-negative undiffere ntiated carcinoma is in accordance with the differing biological behaviour and response to therapy of the two tumour entities.