Clinical value of ERG, TFF3, and SPINK1 for molecular subtyping of prostate cancer

Cancer. 2015 May 1;121(9):1422-30. doi: 10.1002/cncr.29233. Epub 2015 Jan 13.


Background: In view of the marked molecular heterogeneity of prostate cancer (PCa), clinical and pathologic parameters alone may be unreliable for predicting disease outcomes after surgical intervention. The development of biomarkers may be helpful to estimate tumor heterogeneity and stratify patients in terms of their risk of progression. Levels of v-ets avian erythroblastosis virus E26 oncogene homolog (ERG), trefoil factor 3 (TFF3), and serine peptidase inhibitor, Kazal type 1 (SPINK1) are commonly elevated in PCa, but it is unclear whether the evaluation of these 3 markers can help to discriminate patients who will have different clinical outcomes. The authors investigated whether assessment of ERG, TFF3, and SPINK1 expression could help to define clinically relevant, distinct subsets of patients with PCa.

Methods: The cohort consisted of 279 men with PCa who underwent radical prostatectomy at Henri Mondor Hospital. Expression levels of ERG, TFF3, and SPINK1 were evaluated immunohistochemically in the prostatectomy specimens. Potential associations of ERG, TFF3, and SPINK1 with age, prostate-specific antigen (PSA), tumor stage, Gleason score, and biochemical recurrence, defined by PSA failure, were investigated.

Results: Although prognostic significance was not observed for ERG or TFF3, an exclusive pattern of expression was demonstrated for TFF3 and ERG. SPINK1 expression was observed exclusively in a subgroup of cancers that expressed TFF3 (41 of 175 tumors). Moreover, SPINK1 positivity was identified as predictive of biochemical recurrence in univariate (P = .0009) and multivariate (P = .0003) analyses.

Conclusions: The current results suggest that ERG and TFF3 characterize 2 distinct subsets of PCa, with a more aggressive subgroup of TFF3-expressing tumors that express SPINK1. Together, these findings support a rationale of screening for these biomarkers for prognostic purposes and molecular subtyping of the disease.

Keywords: ERG; SPINK1; TFF3; biomarker; prognosis; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carrier Proteins / metabolism*
  • Disease Progression
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Peptides / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Prostate / metabolism
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / surgery
  • Risk
  • Trans-Activators / metabolism*
  • Transcriptional Regulator ERG
  • Trefoil Factor-3
  • Trypsin Inhibitor, Kazal Pancreatic


  • Biomarkers, Tumor
  • Carrier Proteins
  • ERG protein, human
  • Peptides
  • SPINK1 protein, human
  • TFF3 protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Trefoil Factor-3
  • Trypsin Inhibitor, Kazal Pancreatic