NY-ESO-1 expression is tightly linked to TMPRSS2-ERG fusion in prostate cancer

Prostate. 2014 Jul;74(10):1012-22. doi: 10.1002/pros.22816. Epub 2014 May 1.

Abstract

Background: NY-ESO-1 has been suggested as therapeutic cancer vaccine in prostate cancer. This study was undertaken to explore the relationship of NY-ESO-1 with tumor phenotype, biochemical recurrence, and molecular subgroups in hormone-naive prostate cancers.

Methods: NY-ESO-1 immunohistochemistry was analyzed on a tissue microarray containing 11,152 prostate cancer samples. Results were compared to clinically follow-up data, ERG status, and deletions on PTEN, 3p13, 5q21, and 6q15.

Results: NY-ESO-1 expression was absent in benign prostate glands. In prostate cancer, NY-ESO-1 positivity was found 8.8% of our 8,761 interpretable tumors including 5.8% with weak, 2.5% with moderate, and 0.5% with strong expression. There was a threefold higher rate of NY-ESO-1 expression in ERG fusion positive tumors than in ERG negative cancers (P < 0.0001). There was a significant association with early PSA recurrence, which was largely limited to ERG positive cancers. Within the ERG positive subgroup, high NY-ESO-1 expression was associated with early biochemical recurrence (P = 0.0002) and high Gleason grade (P < 0.0001). In ERG negative cancers, NY-ESO-1 expression was also linked to PTEN (P = 0.0012) and 6q15 deletions (P = 0.0005).

Conclusions: Our observations indicate a tight link of NY-ESO-1 expression to ERG activation and (to a lesser extent) PTEN- and 6q15-deletions in prostate cancer. The impact of these interactions on the likelihood of response to immunotherapy is unclear. The prognostic impact of NY-ESO-1 expression is little and not independent of histologic variables.

Keywords: NY-ESO-1; prostate cancer; tissue microarray.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / analysis*
  • Gene Rearrangement
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / analysis*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Oncogene Proteins, Fusion / genetics*
  • PTEN Phosphohydrolase / analysis
  • Prostatic Neoplasms / chemistry*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Tissue Array Analysis
  • Trans-Activators / analysis
  • Transcriptional Regulator ERG

Substances

  • Antigens, Neoplasm
  • CTAG1B protein, human
  • ERG protein, human
  • Membrane Proteins
  • Oncogene Proteins, Fusion
  • TMPRSS2-ERG fusion protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • PTEN Phosphohydrolase
  • PTEN protein, human