Interactions and relationships of PTEN, ERG, SPINK1 and AR in castration-resistant prostate cancer

Histopathology. 2012 Mar;60(4):645-52. doi: 10.1111/j.1365-2559.2011.04116.x. Epub 2012 Jan 19.


Aims: Recently, ETS-related gene (ERG) gene rearrangements, phosphatase tensin homologue (PTEN) deletions and serine protease inhibitor Kazal type 1 (SPINK1) overexpression were investigated as potential markers for molecularly subtyping prostate cancer (PCA). However, their incidence and co-association in castration-resistant PCA (CRPC) has not been characterized fully.

Methods and results: A cohort of 59 CRPC patients was investigated for ERG rearrangements, PTEN deletions and androgen receptor (AR) amplification by fluorescence in-situ hybridization. SPINK1 overexpression was assessed by immunohistochemistry. ERG rearrangements and PTEN deletions were detected in 22 of 53 (41.5%) and 35 of 55 (63.6%) of cases, with 15 of 22 (68.1%) of ERG rearrangements occurring through deletions. SPINK1 overexpression occurred in three of 51 (5.8%) of cases exclusively in non-ERG rearranged and AR amplification was detected in 12 of 49 (24.4%) of cases. Only PTEN deletions showed intrafocal heterogeneity occurring in nine of 35 (25.7%) of cases. PTEN deletions were significantly associated with each of ERG rearrangements occurring by deletions only (P = 0.001), AR amplification (P = 0.002) and SPINK1 overexpression (P = 0.002). None of the SPINK1 overexpressing tumours showed AR amplification (P = 0.005) and all occurred in PTEN deleted foci (P = 0.002).

Conclusion: Te study supports the heterogeneous nature of CRPC and confirms a significant association between PTEN, ERG, AR and SPINK1. Characterizing combined markers will aid in defining PCA subgroups relevant to prognosis contributing to the design of improved therapeutic approaches for CRPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / genetics*
  • Gene Rearrangement
  • Humans
  • Male
  • Orchiectomy
  • PTEN Phosphohydrolase / genetics*
  • Prostate / pathology
  • Prostate / surgery*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Receptors, Androgen / genetics*
  • Trans-Activators / genetics*
  • Transcriptional Regulator ERG
  • Trypsin Inhibitor, Kazal Pancreatic


  • Carrier Proteins
  • ERG protein, human
  • Receptors, Androgen
  • SPINK1 protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Trypsin Inhibitor, Kazal Pancreatic
  • PTEN Phosphohydrolase