Neuroendocrine expression in node positive prostate cancer

Correlation with systemic progression and patient survival

David G. Bostwick, Junqi Qian, Anna Pacelli, Horst Zincke, Michael Blute, Erik J. Bergstralh, Jeffrey M. Slezak, Liang Cheng

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Purpose: Neuroendocrine cells are ubiquitous but uncommon in benign and neoplastic prostate epithelium, and they are considered important for regulating cell growth and differentiation. The predictive value of neuroendocrine immunoreactivity for patient outcome after radical prostatectomy is uncertain. In this study we determined the expression of 2 important neuroendocrine markers, chromogranin and serotonin, in benign epithelium, primary prostate cancer and lymph node metastases, and correlated cellular expression with patient outcome. Materials and Methods: We studied 196 patients with node positive prostate adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical prostatectomy at Mayo Clinic between 1987 and 1992. Mean followup was 6.8 years (range 0.3 to 11). The cellular expression of chromogranin and serotonin in matched samples of benign tissue, primary prostate cancer and lymph node metastases from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, pathological findings (Gleason score, DNA ploidy and cancer volume) and patient outcome, including clinical progression, cancer specific and all cause survival. Results: Chromogranin immunoreactivity was greater in benign prostatic epithelium and primary cancer cases (99% each) than in those of lymph node metastases (37.5%) (pairwise comparisons with metastases p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 6% (median 5%), 6% (median 3%) and 2.2% (median 0%), respectively. Serotonin immunoreactivity was greatest in benign prostate epithelium cases (98.5%) with less in primary cancer (95%) and lymph node metastases (21.5%) (pairwise comparisons p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 2.2% (median 3%), 2.4% (median 2%) and 0.4% (median 0%), respectively. Chromogranin expression was invariably greater than that of serotonin for all 3 diagnostic categories (p <0.0001). There was a marginally significant positive trend in the level of chromogranin expression in benign prostatic epithelium and systemic progression (p = 0.05) but no significant association with cancer specific or all cause survival (p >0.1). No significant association was observed of chromogranin expression in primary cancer or lymph node metastases with any patient outcomes (p >0.1). There was a significant association of the level of serotonin expression in benign prostatic epithelium with cancer specific survival (p = 0.03) but no significant association with systemic progression or all cause survival (p >0.1). There were positive trends in the association of serotonin immunoreactivity in primary cancer with systemic progression (p = 0.09) and cancer specific survival (p = 0.05) but not with all cause survival (p >0.1). No significant association was observed of serotonin expression in lymph node metastases with any patient outcomes (p >0.1). Conclusions: Benign prostatic epithelium and primary prostate cancer express a significantly greater number of chromogranin and serotonin immunoreactive cells than lymph node metastases, suggesting that decreased expression of neuroendocrine markers is involved in cancer progression. However, neuroendocrine expression was marginally useful for predicting the out-come in patients with node positive prostate cancer treated with radical prostatectomy.

Original languageEnglish
Pages (from-to)1204-1211
Number of pages8
JournalJournal of Urology
Volume168
Issue number3
StatePublished - Sep 2002

Fingerprint

Prostatic Neoplasms
Chromogranins
Survival
Serotonin
Neoplasm Metastasis
Lymph Nodes
Epithelium
Neoplasms
Prostatectomy
Prostate
Neuroendocrine Cells
Neoplasm Grading
Ploidies
Lymph Node Excision
Cell Differentiation
Adenocarcinoma
Monoclonal Antibodies
Staining and Labeling
DNA
Growth

Keywords

  • Biological
  • Neoplasm metastasis
  • Neuroendocrine tumors
  • Prostate
  • Prostatic neoplasms
  • Tumor markers

ASJC Scopus subject areas

  • Urology

Cite this

Bostwick, D. G., Qian, J., Pacelli, A., Zincke, H., Blute, M., Bergstralh, E. J., ... Cheng, L. (2002). Neuroendocrine expression in node positive prostate cancer: Correlation with systemic progression and patient survival. Journal of Urology, 168(3), 1204-1211.

Neuroendocrine expression in node positive prostate cancer : Correlation with systemic progression and patient survival. / Bostwick, David G.; Qian, Junqi; Pacelli, Anna; Zincke, Horst; Blute, Michael; Bergstralh, Erik J.; Slezak, Jeffrey M.; Cheng, Liang.

In: Journal of Urology, Vol. 168, No. 3, 09.2002, p. 1204-1211.

Research output: Contribution to journalArticle

Bostwick, DG, Qian, J, Pacelli, A, Zincke, H, Blute, M, Bergstralh, EJ, Slezak, JM & Cheng, L 2002, 'Neuroendocrine expression in node positive prostate cancer: Correlation with systemic progression and patient survival', Journal of Urology, vol. 168, no. 3, pp. 1204-1211.
Bostwick DG, Qian J, Pacelli A, Zincke H, Blute M, Bergstralh EJ et al. Neuroendocrine expression in node positive prostate cancer: Correlation with systemic progression and patient survival. Journal of Urology. 2002 Sep;168(3):1204-1211.
Bostwick, David G. ; Qian, Junqi ; Pacelli, Anna ; Zincke, Horst ; Blute, Michael ; Bergstralh, Erik J. ; Slezak, Jeffrey M. ; Cheng, Liang. / Neuroendocrine expression in node positive prostate cancer : Correlation with systemic progression and patient survival. In: Journal of Urology. 2002 ; Vol. 168, No. 3. pp. 1204-1211.
@article{bb13d63e6c3c4b02bff219bf64ddb89b,
title = "Neuroendocrine expression in node positive prostate cancer: Correlation with systemic progression and patient survival",
abstract = "Purpose: Neuroendocrine cells are ubiquitous but uncommon in benign and neoplastic prostate epithelium, and they are considered important for regulating cell growth and differentiation. The predictive value of neuroendocrine immunoreactivity for patient outcome after radical prostatectomy is uncertain. In this study we determined the expression of 2 important neuroendocrine markers, chromogranin and serotonin, in benign epithelium, primary prostate cancer and lymph node metastases, and correlated cellular expression with patient outcome. Materials and Methods: We studied 196 patients with node positive prostate adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical prostatectomy at Mayo Clinic between 1987 and 1992. Mean followup was 6.8 years (range 0.3 to 11). The cellular expression of chromogranin and serotonin in matched samples of benign tissue, primary prostate cancer and lymph node metastases from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, pathological findings (Gleason score, DNA ploidy and cancer volume) and patient outcome, including clinical progression, cancer specific and all cause survival. Results: Chromogranin immunoreactivity was greater in benign prostatic epithelium and primary cancer cases (99{\%} each) than in those of lymph node metastases (37.5{\%}) (pairwise comparisons with metastases p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 6{\%} (median 5{\%}), 6{\%} (median 3{\%}) and 2.2{\%} (median 0{\%}), respectively. Serotonin immunoreactivity was greatest in benign prostate epithelium cases (98.5{\%}) with less in primary cancer (95{\%}) and lymph node metastases (21.5{\%}) (pairwise comparisons p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 2.2{\%} (median 3{\%}), 2.4{\%} (median 2{\%}) and 0.4{\%} (median 0{\%}), respectively. Chromogranin expression was invariably greater than that of serotonin for all 3 diagnostic categories (p <0.0001). There was a marginally significant positive trend in the level of chromogranin expression in benign prostatic epithelium and systemic progression (p = 0.05) but no significant association with cancer specific or all cause survival (p >0.1). No significant association was observed of chromogranin expression in primary cancer or lymph node metastases with any patient outcomes (p >0.1). There was a significant association of the level of serotonin expression in benign prostatic epithelium with cancer specific survival (p = 0.03) but no significant association with systemic progression or all cause survival (p >0.1). There were positive trends in the association of serotonin immunoreactivity in primary cancer with systemic progression (p = 0.09) and cancer specific survival (p = 0.05) but not with all cause survival (p >0.1). No significant association was observed of serotonin expression in lymph node metastases with any patient outcomes (p >0.1). Conclusions: Benign prostatic epithelium and primary prostate cancer express a significantly greater number of chromogranin and serotonin immunoreactive cells than lymph node metastases, suggesting that decreased expression of neuroendocrine markers is involved in cancer progression. However, neuroendocrine expression was marginally useful for predicting the out-come in patients with node positive prostate cancer treated with radical prostatectomy.",
keywords = "Biological, Neoplasm metastasis, Neuroendocrine tumors, Prostate, Prostatic neoplasms, Tumor markers",
author = "Bostwick, {David G.} and Junqi Qian and Anna Pacelli and Horst Zincke and Michael Blute and Bergstralh, {Erik J.} and Slezak, {Jeffrey M.} and Liang Cheng",
year = "2002",
month = "9",
language = "English",
volume = "168",
pages = "1204--1211",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Neuroendocrine expression in node positive prostate cancer

T2 - Correlation with systemic progression and patient survival

AU - Bostwick, David G.

AU - Qian, Junqi

AU - Pacelli, Anna

AU - Zincke, Horst

AU - Blute, Michael

AU - Bergstralh, Erik J.

AU - Slezak, Jeffrey M.

AU - Cheng, Liang

PY - 2002/9

Y1 - 2002/9

N2 - Purpose: Neuroendocrine cells are ubiquitous but uncommon in benign and neoplastic prostate epithelium, and they are considered important for regulating cell growth and differentiation. The predictive value of neuroendocrine immunoreactivity for patient outcome after radical prostatectomy is uncertain. In this study we determined the expression of 2 important neuroendocrine markers, chromogranin and serotonin, in benign epithelium, primary prostate cancer and lymph node metastases, and correlated cellular expression with patient outcome. Materials and Methods: We studied 196 patients with node positive prostate adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical prostatectomy at Mayo Clinic between 1987 and 1992. Mean followup was 6.8 years (range 0.3 to 11). The cellular expression of chromogranin and serotonin in matched samples of benign tissue, primary prostate cancer and lymph node metastases from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, pathological findings (Gleason score, DNA ploidy and cancer volume) and patient outcome, including clinical progression, cancer specific and all cause survival. Results: Chromogranin immunoreactivity was greater in benign prostatic epithelium and primary cancer cases (99% each) than in those of lymph node metastases (37.5%) (pairwise comparisons with metastases p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 6% (median 5%), 6% (median 3%) and 2.2% (median 0%), respectively. Serotonin immunoreactivity was greatest in benign prostate epithelium cases (98.5%) with less in primary cancer (95%) and lymph node metastases (21.5%) (pairwise comparisons p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 2.2% (median 3%), 2.4% (median 2%) and 0.4% (median 0%), respectively. Chromogranin expression was invariably greater than that of serotonin for all 3 diagnostic categories (p <0.0001). There was a marginally significant positive trend in the level of chromogranin expression in benign prostatic epithelium and systemic progression (p = 0.05) but no significant association with cancer specific or all cause survival (p >0.1). No significant association was observed of chromogranin expression in primary cancer or lymph node metastases with any patient outcomes (p >0.1). There was a significant association of the level of serotonin expression in benign prostatic epithelium with cancer specific survival (p = 0.03) but no significant association with systemic progression or all cause survival (p >0.1). There were positive trends in the association of serotonin immunoreactivity in primary cancer with systemic progression (p = 0.09) and cancer specific survival (p = 0.05) but not with all cause survival (p >0.1). No significant association was observed of serotonin expression in lymph node metastases with any patient outcomes (p >0.1). Conclusions: Benign prostatic epithelium and primary prostate cancer express a significantly greater number of chromogranin and serotonin immunoreactive cells than lymph node metastases, suggesting that decreased expression of neuroendocrine markers is involved in cancer progression. However, neuroendocrine expression was marginally useful for predicting the out-come in patients with node positive prostate cancer treated with radical prostatectomy.

AB - Purpose: Neuroendocrine cells are ubiquitous but uncommon in benign and neoplastic prostate epithelium, and they are considered important for regulating cell growth and differentiation. The predictive value of neuroendocrine immunoreactivity for patient outcome after radical prostatectomy is uncertain. In this study we determined the expression of 2 important neuroendocrine markers, chromogranin and serotonin, in benign epithelium, primary prostate cancer and lymph node metastases, and correlated cellular expression with patient outcome. Materials and Methods: We studied 196 patients with node positive prostate adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical prostatectomy at Mayo Clinic between 1987 and 1992. Mean followup was 6.8 years (range 0.3 to 11). The cellular expression of chromogranin and serotonin in matched samples of benign tissue, primary prostate cancer and lymph node metastases from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, pathological findings (Gleason score, DNA ploidy and cancer volume) and patient outcome, including clinical progression, cancer specific and all cause survival. Results: Chromogranin immunoreactivity was greater in benign prostatic epithelium and primary cancer cases (99% each) than in those of lymph node metastases (37.5%) (pairwise comparisons with metastases p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 6% (median 5%), 6% (median 3%) and 2.2% (median 0%), respectively. Serotonin immunoreactivity was greatest in benign prostate epithelium cases (98.5%) with less in primary cancer (95%) and lymph node metastases (21.5%) (pairwise comparisons p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 2.2% (median 3%), 2.4% (median 2%) and 0.4% (median 0%), respectively. Chromogranin expression was invariably greater than that of serotonin for all 3 diagnostic categories (p <0.0001). There was a marginally significant positive trend in the level of chromogranin expression in benign prostatic epithelium and systemic progression (p = 0.05) but no significant association with cancer specific or all cause survival (p >0.1). No significant association was observed of chromogranin expression in primary cancer or lymph node metastases with any patient outcomes (p >0.1). There was a significant association of the level of serotonin expression in benign prostatic epithelium with cancer specific survival (p = 0.03) but no significant association with systemic progression or all cause survival (p >0.1). There were positive trends in the association of serotonin immunoreactivity in primary cancer with systemic progression (p = 0.09) and cancer specific survival (p = 0.05) but not with all cause survival (p >0.1). No significant association was observed of serotonin expression in lymph node metastases with any patient outcomes (p >0.1). Conclusions: Benign prostatic epithelium and primary prostate cancer express a significantly greater number of chromogranin and serotonin immunoreactive cells than lymph node metastases, suggesting that decreased expression of neuroendocrine markers is involved in cancer progression. However, neuroendocrine expression was marginally useful for predicting the out-come in patients with node positive prostate cancer treated with radical prostatectomy.

KW - Biological

KW - Neoplasm metastasis

KW - Neuroendocrine tumors

KW - Prostate

KW - Prostatic neoplasms

KW - Tumor markers

UR - http://www.scopus.com/inward/record.url?scp=0036719358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036719358&partnerID=8YFLogxK

M3 - Article

VL - 168

SP - 1204

EP - 1211

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 3

ER -