PCA3 and PSA gene activity correlates with the true tumor cell burden in prostate cancer lymph node metastases

Cancer Biomark. 2015;15(3):311-6. doi: 10.3233/CBM-150461.

Abstract

Background: Extent of pelvic lymph node (LN) dissemination is a critical prognostic feature for patients with prostate cancer (PCa) maintaining extended pelvic lymphadenectomy (LAD) as the gold standard for LN-staging. Unfortunately, conventional histopathological assessment may miss micrometastasis and recently presented immunocytochemical approach of the single cell analysis is still intricate.

Objective: To comparatively assess the potential of Prostate cancer gene 3 (PCA3) and prostate specific antigene (PSA) to perform as markers for tumor cell load.

Methods: Patients with high risk PCa for LN metastasis undergoing either a sentinel LN-guided staging LAD or retropubic radical prostatectomy with sentinel-guided pelvic LN dissection were included. LNs were investigated by routine histopathology. Tumor cell load was quantified by %immunocytochemistry. immunocytochemical single cell analysis. Gene activity was determined by qRT-PCR.

Results: Twenty four out of 226 LNs were positive in routine histopathology and 51 in single cell analysis. PSA mRNA level correlated with tumor cell density in patients with a positive immunocytochemistry. Gene activity of PCA3 was upregulated in metastatic LNs and correlated with tumor cell density in patients with tumor-invaded LNs as detected by immunocytochemistry.

Conclusions: PCA3 gene expression discriminates LN metastasis and might outperform PSA gene activity in reflecting tumor cell burden in pelvic LNs of PCa patients.

Keywords: PCA3; PSA; Prostate cancer; lymph node metastases; molecular marker; tumor cell load.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / secondary
  • Antigens, Neoplasm / genetics*
  • Biomarkers, Tumor / genetics*
  • Humans
  • Lymph Node Excision
  • Lymphatic Metastasis
  • Male
  • Prostate-Specific Antigen / genetics*
  • Prostatectomy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Tumor Burden

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • RNA, Messenger
  • prostate cancer antigen 3, human
  • Prostate-Specific Antigen