Neuroendocrine Differentiation in Metastatic Conventional Prostate Cancer Is Significantly Increased in Lymph Node Metastases Compared to the Primary Tumors

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.

An Update on the Prognostic and Predictive Serum Biomarkers in Metastatic Prostate Cancer

“…Neuroendocrine prostate cancer (NEPC) is uncommon and is associated with low PSA secretion and loss of androgen receptor expression. De novo small cell prostate cancer is an aggressive histological variant and is very rare in untreated patients (<1%) [ 37 , 38 ].…”

Advances in Biomarkers for PCa Diagnostics and Prognostics—A Way towards Personalized Medicine

“…Another survey by Genitsch et al [ 33 ] also tested the neuroendocrine differentiation (NED) by Chromogranin A expression in lymph node metastases, as well as primary tumors, from 119 consecutive PCa patients. 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%).…”

“…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%). However, in primary tumors and nodal metastases, tumor areas with higher Gleason patterns tended to display a higher NED, but no significance was reached [ 33 ].…”

“…Two of the four reviews further summarize biomarkers for PCa diagnostic [ 27 ] or active surveillance [ 28 ] while the other two reviews have special topics like nanoparticles as theranostic vehicles [ 29 ] or PCa stem cells [ 30 ]. Four working groups published results by using immunohistochemistry in prostate, lymph node or bone tissue [ 31 , 32 , 33 , 34 ]. This Special Issue also covered studies on seminal plasma biomarkers [ 35 ], improved PET contrast between osteolytic and osteoblastic bone metastatic lesions with fasting [ 36 ] and the impact of the blood collection tube and storage time on CTC-mRNA (AR-V7) analysis [ 37 ].…”

Cell-Free DNA and Neuromediators in Detecting Aggressive Variant Prostate Cancer

“…Sequential biopsies of metastases prior to several lines of therapy for the detection of aggressive variant transformation are difficult to implement in daily practice. Several studies show a correlation between neuromediator levels, tissue expression, and neuroendocrine activity in patients with prostate cancer [3,6,7,8]. Therefore, the dynamics of neuromediators could be used as a screening tool for patients at risk for aggressive variants like SCNC transformation before and during therapy.…”