Neuroendocrine differentiation in castration-resistant prostate cancer: a systematic diagnostic attempt

Clin Genitourin Cancer. 2012 Sep;10(3):164-73. doi: 10.1016/j.clgc.2011.12.004. Epub 2012 Mar 7.

Abstract

Background: Assessing the neuroendocrine (NE) pattern in castration-resistant prostate cancer (CRPC) may prove useful in selecting potential responders to target therapies such as somatostatin analogues. The aim of this study was to define a panel of markers or examinations appropriate to characterize NE differentiation (NED).

Methods: Forty-seven patients with CRPC underwent a systematic diagnostic attempt to characterize the NE phenotype using a plasma blood test for chromogranin A (CgA) and immunohistochemical staining of needle biopsy-obtained specimens (CgA, somatostatin receptor 2 [SSTR2], Ki-67, and androgen receptors). In a subgroup of 26 patients, somatostatin receptor scintigraphy using (111)In-DTPA-d-Phe octreotide (octreotide scintigraphy; Octreoscan, Covidien, Hazelwood, MO) was also performed.

Results: NED was found in 85.1% of patients (if serum CgA, tissular CgA, and tissular SSTR2 were considered separately: 54%, 67%, and 58%, respectively). Only 15% of the 26-patient subgroup had an abnormal octreotide scintigraphy result. Although p-CgA and t-CgA were associated with more aggressive disease with a worse prognosis, patients with positive tissular SSTR2 staining had longer overall survival (OS).

Conclusion: This systematic approach to explore the NED in a quite homogeneous group of patients with CRPC seems reproducible and appropriate. Further investigations are required to validate this panel and better characterize potential responders to targeted therapy.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Chromogranin A / blood*
  • Chromogranin A / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasms, Hormone-Dependent / blood
  • Neoplasms, Hormone-Dependent / mortality
  • Neoplasms, Hormone-Dependent / pathology*
  • Neuroendocrine Tumors / blood
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology*
  • Orchiectomy
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / metabolism
  • Receptors, Somatostatin / metabolism

Substances

  • Biomarkers, Tumor
  • Chromogranin A
  • Receptors, Androgen
  • Receptors, Somatostatin
  • SSTR2 protein, human