Are biomarkers evaluated in biopsy specimens predictive of prostate cancer aggressiveness?

J Cancer Res Clin Oncol. 2016 Jan;142(1):201-12. doi: 10.1007/s00432-015-2015-1. Epub 2015 Jul 26.

Abstract

Purpose: To evaluate biomarkers involved in biological pathways for prostate cancer (PCa) progression, measured in biopsy specimens, in order to distinguish patients at higher risk for fatal PCa and thus improve the initial management of disease.

Methods: Retrospective case-control study. In 129 PCa patients who underwent ultrasound-guided needle prostate biopsy and subsequent radical prostatectomy from 1987 to 1999 at the University Hospital of Careggi, we evaluated: (1) mRNA expression of the serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG); (2) expression of matrix metalloproteinases (MMP)-2 and 9 (epithelial and stromal); (3) expression of androgen receptor; (4) expression of prognostic marker Ki67 (MIB1); (5) presence and typing of human papilloma virus; (6) DNA methylation of CpG islands of several genes involved in PCa progression.

Results: The cohort consists of 38 cases (patients with PCa and died of PCa within 10 years from diagnosis) and 91 controls (patients with PCa but alive 10 years after diagnosis). Gleason bioptic score, epithelial MMP expression and SERPINB5 methylation correlated with statistically significant increase in death risk OR. Compared with patients with high level of MMP, patients with low level of MMP had OR for specific death 4.78 times higher (p = 0.0066). After adjustment for age and Gleason score, none of the investigated biomarkers showed increased OR for PCa death.

Conclusions: Our preliminary results suggest that evaluation, in prostate biopsy specimens, of a panel of biomarkers known to be involved in PCa progression is poorly indicative of tumor outcome.

Keywords: Biomarker; HPV; Metalloproteinase; Prostate biopsy; Prostate cancer; TMPRSS2:ERG.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Case-Control Studies
  • DNA Methylation*
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Serpins / genetics
  • Serpins / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcriptional Regulator ERG

Substances

  • AR protein, human
  • Biomarkers, Tumor
  • ERG protein, human
  • RNA, Messenger
  • Receptors, Androgen
  • SERPIN-B5
  • Serpins
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9