Neuroendocrine differentiation in prostate cancer

In numerous recent studies attention has been focused to neuroendocrine differentiation (NED) in prostate cancer (PC). Focal NED is present in almost all PCs, but it is prominent in only 5-10% of the carcinomas. The prognostic significance of focal NED in PC is controversial, but current evidence suggests its influence on the onset and/or conversion of hormone resistant tumor phenotype. The aim of this study was to evaluate the relationship between NED status, based only on immunohistochemical use of neuroendocrine (NE) markers, with PC grade and stage, and preoperative serum levels of prostate-specific antigen (PSA).

The study included the biopsy material of 73 untreated PC patients (pts.) obtained by transurethral resection (TUR) (37 pts.), and radical retropubic prostatectomy (RRP) (36 pts.). Two representative tissue samples (typically the block containing the largest amount of neoplasm) were selected for immunohistochemical (IMM) staining. NE cells were identified using a panel of IMM markers: chromogranin A, neuron-specific enolase, and serotonin. The level of PC exocrine differentiation was detected by monoclonal antibodies against PSA.

Significant expression of NE cells was demonstrated in 26 (70.2%) pts. with PC after TUR. In this group, serum preoperative PSA values ranged from 0.1 to 9.6 ng/ml. The majority of pts. with NED had low differentiated PC with Gleason grade score (GGS) > 7, and normal PSA values below 4 ng/ml (77%), in clinical stage D (54%). Statistically significant correlation (p<0.01) of positive NED with higher stage and grade and low PSA values was established. Among the pts. with localized PC in whom RRP was performed (n=36), significant expression of NE cells was found in 15 pts. (41.7%), 8 (53.3%) in pT2 stage, and 7 (46.7%) in pT3 stage. Significant correlation between NED with preoperative PSA values and stage of PC in pts. with RRP was not found.

We demonstrated the significant NED in poorly differentiated PC in patients in the advanced stage of the disease. The expression of NED in organ-confined PC did not correlate with tumor stage, but it correlated with tumor grade (GGS < or = 7).