DNA repair and replication proteins as prognostic markers in melanoma

Histopathology. 2013 Jan;62(2):343-50. doi: 10.1111/j.1365-2559.2012.04362.x. Epub 2012 Sep 28.

Abstract

Aims: Elevated expression of DNA repair and replication genes has been reported in thick, non-fixed primary melanomas that subsequently went on to metastasize, when compared to non-recurrent primary tumours. This increased expression could contribute to the extreme resistance shown by melanoma to DNA-damaging chemotherapeutics. We have investigated the hypothesis that levels of key DNA repair and replication proteins are prognostic biomarkers in melanoma.

Methods and results: We used a tissue microarray containing samples from all stages of melanomagenesis to investigate the hypothesis that levels of key DNA repair and replication proteins are prognostic biomarkers in a larger, more representative and readily available set of fixed primary melanomas. High expression of topoisomerase IIα (TOP2A), that relieves torsional stress during DNA replication, and XRCC5 (Ku80), required for DNA double-strand break repair, were associated with significantly worse survival.

Conclusions: Two (XRCC5 and TOP2A) of seven DNA repair and replication proteins studied were prognostic for melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism
  • DNA Helicases / metabolism*
  • DNA Repair*
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Ku Autoantigen
  • Lymph Nodes / pathology
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / mortality
  • Melanoma / secondary*
  • Poly-ADP-Ribose Binding Proteins
  • Prognosis
  • Proportional Hazards Models
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology*
  • Survival Rate
  • Tissue Array Analysis
  • United Kingdom / epidemiology

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • DNA Helicases
  • XRCC5 protein, human
  • Ku Autoantigen
  • DNA Topoisomerases, Type II
  • TOP2A protein, human