Abstract
Introduction: It is now recognized that androgen deprivation therapy (ADT) can induce neuroendocrine (NE) differentiation (NED) in prostate cancer (PCa) as well as histologically distinct NE cancer in >25% of castrate resistant prostate cancer (CRPCa). Neuroendocrine cells, which are present but rare in the normal prostate, secrete growth factors but the mechanism of normal NED in the developing prostate is largely unknown. We hypothesize that the neuroendocrine phenotype, seen in CRPCa, recaptures events that occurs during normal prostatic development in response to the androgens. The purpose of these experiments is to determine if NED occurs in the development of the normal mouse prostate in response to androgen.
Methods: 8-10 week old male mice (n=7 per group) were castrated and 2 weeks post-castration were treated with androgens (DHT) or oil (control), and then euthanized 1, 2 or 4 hours after treatment. Prostate lobes were then dissected, analyzed by immunohistochemistry for synaptophysin, a marker of NED, and scored blindly (Table 1). Intensity and distribution were then summed and analyzed using the Mann-Whitney test.
Score Intensity Distribution
0 No expression No expression
1 Weak Antibody expression in 0-33% of epithelial cells
2 Mild Antibody expression in 33%-66% of epithelial cells
3 Strong Antibody expression in 66%- 100% of epithelial cells
Table 1: Immunohistochemistry scoring system
Results: No significant difference in synaptophysin staining was found in the epithelium between oil and DHT treated samples in the anterior, dorsal, and lateral prostate. There was a significant difference in synaptophysin staining found between oil and DHT treated samples at the 1 hour time point in the ventral prostate (p < 0.05). This difference disappeared in subsequent time points in the ventral prostate.
Conclusion: Androgens induce rapid and transient NED in the murine ventral prostate epithelium, indicated by a spike in synaptophysin at the 1 hour time point. By 2 hours, there is no significant difference in synaptophysin staining between the oil and DHT treated samples. This transient elevation in a NED marker is only observed in the ventral lobe. This indicates that CRPCa may recapture events that occur in the growth of the normal prostate.
Citation Format: Danielle N. Sanders, Magdalena Grabowska, Robert Matusik. Neuroendocrine differentiation in prostate cancer and development. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B23.
RSS Feeds