Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence

Mod Pathol. 2013 May;26(5):733-42. doi: 10.1038/modpathol.2012.206. Epub 2012 Nov 30.

Abstract

The aim of this study was to determine whether cysteine-rich secretory protein 3 (CRISP3) expression is linked to clinically or molecularly relevant subgroups of prostate cancer. A tissue microarray representing samples from >10,000 prostate cancers from radical prostatectomy specimens with clinical follow-up data were analyzed for CRISP3 expression by immunohistochemistry. CRISP3 expression was also compared with key genomic alterations of prostate cancer. CRISP3 staining was found as weak in 15%, moderate in 8.5%, and strong in 7.2% of prostate cancers, whereas no expression was detected in normal prostate. Strong CRISP3 expression was linked to advanced tumor stage, high Gleason score, and positive surgical margin status (P<0.0001 each). There was a marked accumulation of high CRISP3 expression in PTEN-deleted ERG-positive tumors (P<0.0001). A total of, 21.7% of ERG-positive and PTEN-deleted cancers had strong CRISP3 expression, but only 10.4% of ERG-positive cancers without PTEN deletion (P<0.0001). The rate of high CRISP3 expression was 2.5% in ERG-negative cancers (P=0.0001; vs ERG-positive cancers). Accordingly, CRISP3 overexpression was associated with early prostate-specific antigen recurrence in all tumors (P=0.0013) as well as in ERG-negative (P=0.004) and ERG-positive cancers (P=0.0318). CRISP3 expression did not retain prognostic significance in models also involving PTEN deletions. Strong CRISP3 expression is associated with unfavorable tumor phenotype and early recurrence in prostate cancers. The tight link of strong CRISP3 expression to the ERG fusion-positive prostate cancers with PTEN deletions provides further evidence for the existence of molecularly distinct subgroups of prostate cancers.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism*
  • Oncogene Proteins, Fusion / genetics
  • PTEN Phosphohydrolase / genetics
  • Prognosis
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Salivary Proteins and Peptides / analysis
  • Salivary Proteins and Peptides / biosynthesis*
  • Seminal Plasma Proteins / analysis
  • Seminal Plasma Proteins / biosynthesis*
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • CRISP3 protein, human
  • Oncogene Proteins, Fusion
  • Salivary Proteins and Peptides
  • Seminal Plasma Proteins
  • TMPRSS2-ERG fusion protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Prostate-Specific Antigen