Chromogranin A expression in patients with hormone naïve prostate cancer predicts the development of hormone refractory disease

J Urol. 2007 Sep;178(3 Pt 1):838-43; quiz 1129. doi: 10.1016/j.juro.2007.05.018. Epub 2007 Jul 16.

Abstract

Purpose: We assessed chromogranin A as a tissue biomarker in prostate needle biopsies or as a plasma biomarker, a risk factor for hormone refractory prostate cancer.

Materials and methods: A total of 211 patients with newly diagnosed prostate cancer treated with luteinizing hormone releasing hormone analogues constituted the study cohort. Univariate and multivariate Cox regression analyses were used to assess the predictive role of tissue and plasma chromogranin A expression.

Results: Chromogranin A expression in less than 30% or in 30% or more tumor cells was significantly associated with a shorter time to hormone refractory disease on univariate analysis (HR 2.0, 95% CI 1.3-3.1 and HR 6.0, 95% CI 2.7-12.9), or on multivariate analysis after adjusting for Gleason score, serum prostate specific antigen and disease stage (HR 1.7, 95% CI 1.0-2.8 and HR 3.9, 95% CI 1.7-9.0), respectively. Plasma chromogranin A measured at baseline (HR 3.0, 95% CI 1.8-5.2), and after 1 year (HR 5.8, 95% CI 3.1-10.1) and 2 years (HR 3.5, 95% CI 1.6-7.6), was predictive of hormone refractory risk confirming the tissue results. Plasma as well as tissue chromogranin A expression negatively correlated with overall survival.

Conclusions: Chromogranin A expression in prostate cancer biopsies is an independent predictive factor of hormone refractory disease in patients with newly diagnosed prostate cancer on early androgen deprivation therapy. Plasma chromogranin A is also a reliable predictive marker and the predictive significance is maintained over time. These results deserve validation in another data set.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism*
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Chromogranin A / analysis*
  • Gonadotropin-Releasing Hormone / analogs & derivatives
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / metabolism
  • Prognosis
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Chromogranin A
  • Gonadotropin-Releasing Hormone