Deletion of 8p is an independent prognostic parameter in prostate cancer

Oncotarget. 2017 Jan 3;8(1):379-392. doi: 10.18632/oncotarget.13425.

Abstract

Deletion of chromosome 8p is the second most frequent genomic alteration in prostate cancer. To better understand its clinical significance, 8p deletion was analyzed by fluorescence in-situ hybridization on a prostate cancer tissue microarray. 8p deletion was found in 2,581 of 7,017 cancers (36.8%), and was linked to unfavorable tumor phenotype. 8p deletion increased from 29.5% in 4,456 pT2 and 47.8% in 1,598 pT3a to 53.0% in 931 pT3b-pT4 cancers (P < 0,0001). Deletions of 8p were detected in 25.5% of 1,653 Gleason ≤ 3 + 3, 36.6% of 3,880 Gleason 3 + 4, 50.2% of 1,090 Gleason 4 + 3, and 51.1% of 354 Gleason ≥ 4 + 4 tumors (P < 0,0001). 8p deletions were strongly linked to biochemical recurrence (P < 0.0001) independently from established pre- and postoperative prognostic factors (P = 0.0100). However, analysis of morphologically defined subgroups revealed, that 8p deletion lacked prognostic significance in subgroups with very good (Gleason ≤ 3 + 3, 3 + 4 with ≤ 5% Gleason 4) or very poor prognosis (pT3b, Gleason ≥ 8, pN1). 8p deletions were markedly more frequent in cancers with (53.5%) than without PTEN deletions (36.4%; P < 0,0001) and were slightly more frequent in ERG-positive (40.9%) than in ERG-negative cancers (34.7%, P < 0.0001) due to the association with the ERG-associated PTEN deletion. Cancers with 8p/PTEN co-deletions had a strikingly worse prognosis than cancers with deletion of PTEN or 8p alone (P ≤ 0.0003). In summary, 8p deletion is an independent prognostic parameter in prostate cancer that may act synergistically with PTEN deletions. Even statistically independent prognostic biomarkers like 8p may have limited clinical impact in morphologically well defined high or low risk cancers.

Keywords: NKX3.1; PTEN; TMPRSS2:ERG; prostate cancer; tissue microarray.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 8
  • Disease Progression
  • Follow-Up Studies
  • Gene Deletion
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence / methods
  • Kallikreins / blood*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics*
  • Prognosis
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / pathology
  • Tissue Array Analysis / methods
  • Transcriptional Regulator ERG / metabolism

Substances

  • Biomarkers, Tumor
  • ERG protein, human
  • Transcriptional Regulator ERG
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen

Supplementary concepts

  • Chromosome 8, monosomy 8p