Abstract
Neuroendocrine serum markers released from prostate cancers have been proposed for monitoring disease and predicting survival. However, neuroendocrine differentiation (NED) in various tissue compartments of metastatic prostate cancer is poorly described and its correlation with specific tumor features is unclear. NED was determined by Chromogranin A expression on immunostains from a tissue microarray of 119 nodal positive, hormone treatment-naïve prostate cancer patients who underwent radical prostatectomy and extended lymphadenectomy. NED in the primary cancer and in the metastases was correlated with tumor features and survival. The mean percentage of NED cells increased significantly (p < 0.001) from normal prostate glands (0.4%), to primary prostate cancer (1.0%) and nodal metastases (2.6%). In primary tumors and nodal metastases, tumor areas with higher Gleason patterns tended to display a higher NED, although no significance was reached. The same was observed in patients with a larger primary tumor volume and higher total size and number of metastases. NED neither in the primary tumors nor in the metastases predicted outcome significantly. Our data suggest that (a) increasing levels of neuroendocrine serum markers in the course of prostate cancer might primarily derive from a poorly differentiated metastatic tumor component; and (b) NED in conventional hormone-naïve prostate cancers is not significantly linked to adverse tumor features.
Highlights
The current World Health Organization (WHO) classification of prostate neoplasms with neuroendocrine (NE) differentiation (NED) comprises of: (1) adenocarcinomas with neuroendocrine differentiation (NED); (2) well-differentiated NE tumors; (3) small-cell NE carcinomas; and (4) large cell NE carcinomas [1]
A higher proportion of 92% of primary tumors displayed any positivity for Chromogranin A compared to lymph node metastases with a positive expression in 77%
When the density of NE cancer cells was recorded, a progressive and significant increase in expression from non-neoplastic prostate glands (0.4% mean of Chromogranin A positive cells) to primary tumors (1.0%) and lymph node metastases (2.6%; p < 0.001) was noted for Chromogranin A (Figure 1A)
Summary
The current World Health Organization (WHO) classification of prostate neoplasms with neuroendocrine (NE) differentiation (NED) comprises of: (1) adenocarcinomas with NED; (2) well-differentiated NE tumors (carcinoid); (3) small-cell NE carcinomas; and (4) large cell NE carcinomas [1]. Neuropeptides released from the NE prostate cancer cells may appear in the circulation [6] These serum markers have recently attracted considerable attention for their ability to monitor disease [6,11] and predict survival [12,13]. Serum levels of Chromogranin A are significantly higher in metastatic compared to non-metastatic prostate cancers [14]. Despite this interest in NE serum markers, little is known about the distribution of their source, which are the NE tumor cells, in the various growth patterns and in the metastases of prostate cancer. We more accurately describe the extent of NED in the different tissue compartments of metastasizing prostate cancer, and determine its correlations with different tumor features and survival
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