V-ets erythroblastosis virus E26 oncogene homolog (avian)/Trefoil factor 3/high-molecular-weight cytokeratin triple immunostain: A novel tissue-based biomarker in prostate cancer with potential clinical application Academic Article uri icon


MeSH Major

  • Adenocarcinoma
  • Biomarkers, Tumor
  • Keratins
  • Peptides
  • Prostatic Neoplasms
  • Trans-Activators


  • Trefoil factor 3 (TFF3) is associated with various cancers and overexpressed in a subset of prostate cancers. Functional studies suggest that v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) down-regulates TFF3 expression in hormone-na├»ve prostate cancer. To characterize this inverse relationship, we developed a triple immunostain encompassing ERG, TFF3, and high-molecular-weight cytokeratin. Triple stain was performed on 96 tumors and 52 benign cases represented in tissue microarrays. Distinct ERG and TFF3 protein was expressed in 45% (43/96) and 36% (35/96) of prostate cancers, respectively. Coexpression was observed in 5% (5/96) of tumor cases, and 24% (23/96) did not express ERG or TFF3. The inverse expression of ERG and TFF3 was significant (P < .0001), with 57% (30/53) of ERG-negative tumors demonstrating TFF3 expression. Sensitivity and specificity of combined ERG and TFF3 expression in detecting prostate cancer were 76% and 96%, respectively. The feasibility of triple immunostain protocol was validated in a set of 76 needle biopsies. The application of this multiplex in situ biomarker for molecular characterization of prostate cancer and as a supplemental diagnostic and prognostic tool in prostate needle biopsies should be further explored.

publication date

  • October 2013



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.humpath.2013.05.010

PubMed ID

  • 23856515

Additional Document Info

start page

  • 2282

end page

  • 92


  • 44


  • 10