Evidence for molecular differences in prostate cancer between African American and Caucasian men

Clin Cancer Res. 2014 Sep 15;20(18):4925-34. doi: 10.1158/1078-0432.CCR-13-2265. Epub 2014 Jul 23.

Abstract

Purpose: The aim of this study was to compare the frequency of ERG rearrangement, PTEN deletion, SPINK1 overexpression, and SPOP mutation in prostate cancer in African American and Caucasian men.

Experimental design: Dominant tumor nodules from radical prostatectomy specimens of 105 African American men (AAM) were compared with 113 dominant nodules from Caucasian men (CaM). Clinical and pathologic characteristics of the two groups were similar. SPINK1 overexpression was evaluated by immunohistochemistry, ERG rearrangement and PTEN deletion by FISH, and SPOP mutation by Sanger sequencing.

Results: ERG rearrangement was identified in 48 of 113 tumors (42.5%) in CaM and 29 of 105 tumors (27.6%) in AAM (P = 0.024). PTEN deletion was seen in 19 of 96 tumors (19.8%) in CaM and 7 of 101 tumors (6.9%) in AAM (P = 0.011). SPINK1 overexpression was present in 9 of 110 tumors (8.2%) in CaM and 25 of 105 tumors (23.4%) in AAM (P = 0.002). SPOP mutation was identified in 8 of 78 (10.3%) tumors in CaM and 4 of 88 (4.5%) tumors in AAM (P = 0.230). When adjusted for age, body mass index, Gleason score, and pathologic stage, ERG rearrangement and SPINK1 overexpression remain significantly different (P = 0.018 and P = 0.008, respectively), and differences in PTEN deletion and SPOP mutation approach significance (P = 0.061 and P = 0.087, respectively).

Conclusions: Significant molecular differences exist between prostate cancers in AAM and CaM. SPINK1 overexpression, an alteration associated with more aggressive prostate cancers, was more frequent in AAM, whereas ERG rearrangement and PTEN deletion were less frequent in this cohort. Further investigation is warranted to determine whether these molecular differences explain some of the disparity in incidence and mortality between these two ethnic groups.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Americans / genetics
  • Aged
  • Biomarkers, Tumor / genetics*
  • Carrier Proteins / genetics
  • Gene Deletion
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics
  • PTEN Phosphohydrolase / genetics
  • Prostatic Neoplasms / ethnology*
  • Prostatic Neoplasms / genetics*
  • Repressor Proteins / genetics
  • Retrospective Studies
  • Trans-Activators / genetics
  • Transcriptional Regulator ERG
  • Trypsin Inhibitor, Kazal Pancreatic
  • Whites / genetics

Substances

  • Biomarkers, Tumor
  • Carrier Proteins
  • ERG protein, human
  • Nuclear Proteins
  • Repressor Proteins
  • SPINK1 protein, human
  • SPOP protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Trypsin Inhibitor, Kazal Pancreatic
  • PTEN Phosphohydrolase
  • PTEN protein, human