Diagnostic biomarkers of prostate cancer

Scand J Urol Nephrol. 2011 Feb;45(1):60-7. doi: 10.3109/00365599.2010.526141. Epub 2010 Nov 1.

Abstract

Objective: Diagnostic tissue biomarkers for prostate cancer (PC) include basal cell markers and α-methylacyl-coenzyme A-racemase (AMACR), often used in combination. Their sensitivity and specificity are not perfect and there is a need for additional diagnostic biomarkers for PC in cases that are difficult to diagnose on routine stained sections.

Material and methods: This study investigated the diagnostic accuracy of three novel tissue biomarkers for PC found through a search in the Human Protein Atlas database ( www.proteinatlas.com ): somatic cytochrome c (CYCS), intestinal cell kinase (ICK) and inhibitor of nuclear factor-κB kinase subunit beta (IKBKB), and compared the results with AMACR. A tissue microarray was constructed from 40 consecutive radical prostatectomy (RP) specimens including benign prostatic tissue, atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and PC. Immunoreactivity was scored based on staining intensity and extent. Real-time polymerase chain reaction (PCR) was performed on malignant and benign frozen tissue samples from 32 RP specimens.

Results: All four biomarkers showed a stronger expression in PC and HGPIN than in benign tissue (p < 0.001). The highest diagnostic accuracy for PC was achieved with ICK and AMACR at 97%. The area under the curve for CYCS, ICK, IKBKB and AMACR was 0.859, 0.997, 0.865 and 0.983, respectively. The presence of mRNA transcripts of the genes was confirmed by real-time PCR in benign and malignant prostatic tissue.

Conclusions: AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Cytochromes c / metabolism*
  • Humans
  • I-kappa B Kinase / metabolism*
  • Male
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Intraepithelial Neoplasia / metabolism
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / metabolism
  • Racemases and Epimerases / metabolism*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • Cytochromes c
  • CILK1 protein, human
  • Protein Serine-Threonine Kinases
  • I-kappa B Kinase
  • IKBKB protein, human
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase