Operator dependent choice of prostate cancer biopsy has limited impact on a gene signature analysis for the highly expressed genes IGFBP3 and F3 in prostate cancer epithelial cells

PLoS One. 2014 Oct 8;9(10):e109610. doi: 10.1371/journal.pone.0109610. eCollection 2014.


Background: Predicting the prognosis of prostate cancer disease through gene expression analysis is receiving increasing interest. In many cases, such analyses are based on formalin-fixed, paraffin embedded (FFPE) core needle biopsy material on which Gleason grading for diagnosis has been conducted. Since each patient typically has multiple biopsy samples, and since Gleason grading is an operator dependent procedure known to be difficult, the impact of the operator's choice of biopsy was evaluated.

Methods: Multiple biopsy samples from 43 patients were evaluated using a previously reported gene signature of IGFBP3, F3 and VGLL3 with potential prognostic value in estimating overall survival at diagnosis of prostate cancer. A four multiplex one-step qRT-PCR test kit, designed and optimized for measuring the signature in FFPE core needle biopsy samples was used. Concordance of gene expression levels between primary and secondary Gleason tumor patterns, as well as benign tissue specimens, was analyzed.

Results: The gene expression levels of IGFBP3 and F3 in prostate cancer epithelial cell-containing tissue representing the primary and secondary Gleason patterns were high and consistent, while the low expressed VGLL3 showed more variation in its expression levels.

Conclusion: The assessment of IGFBP3 and F3 gene expression levels in prostate cancer tissue is independent of Gleason patterns, meaning that the impact of operator's choice of biopsy is low.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artifacts
  • Biopsy, Large-Core Needle / methods*
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Male
  • Neoplasm Grading
  • Platelet Factor 3 / genetics*
  • Prognosis
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Transcription Factors / genetics


  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Transcription Factors
  • VGLL3 protein, human
  • Platelet Factor 3

Grant support

This work was financed by Uppsala Bio (http://www.uppsalabio.com/), the Swedish Cancer Society (http://www.cancerfonden.se/sv/Information-in-English/), the King Gustaf V Jubilee Foundation (http://www.rahfo.se/Metamenyn/In-English/), and the Stockholm county council (http://www.sll.se/om-landstinget/Information-in-English1/). The funders provided support in the form of salaries for Zhuochun Peng, Karolinska Institutet, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.