RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma.

  • Tennstedt P
  • Fresow R
  • Simon R
 et al. 
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RAD51 is the central protein in the homologous recombination pathway and is therefore of great relevance in terms of both therapy resistance as well as genomic stability. By using a tissue microarray analysis of 1,213 biopsies taken from colorectal adenocarcinomas (CRCs), we investigated whether RAD51 expression can be used as a prognostic marker as well as potential associations between this and the expression of other proteins known to be related to CRC. Strong RAD51 expression was observed in 1% of CRC, moderate in 11%, weak in 34% and no expression in 44%. No correlation was found between RAD51 expression and clinicopathological parameters. RAD51 expression correlated significantly (p = 0.001) with overall survival, with a median survival of 11 months for patients with strong, 46 with moderate, 76 with weak and 68 with negative expression. Multivariate analyses revealed that in addition to tumor stage (p < 0.0001) and nodal status (p < 0.0001), RAD51 expression is also an independent prognostic parameter (p = 0.011). Strong RAD51 expression was found to be associated with the loss of the two DNA mismatch repair proteins MSH (p = 0.0003), MLH (p = 0.002) and β-catenin (p = 0.012) as well as with elevated p21 (p = 0.003) and EGFR expression (p = 0.0001). However, a correlation with overall survival could only be found for EGFR expression (p = 0.008), although no added benefit in risk stratification could be determined when evaluated together with RAD51. Overexpression of RAD51 is a predictor of poor outcome in CRC. This finding indicated the promise of future studies using RAD51 as a prognostic marker and therapeutic target.

Author-supplied keywords

  • Adenocarcinoma
  • Adenocarcinoma: metabolism
  • Adenocarcinoma: mortality
  • Adenocarcinoma: radiotherapy
  • Aged
  • Biomarkers, Tumor
  • Biomarkers, Tumor: metabolism
  • Colorectal Neoplasms
  • Colorectal Neoplasms: metabolism
  • Colorectal Neoplasms: mortality
  • Colorectal Neoplasms: radiotherapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Rad51 Recombinase
  • Rad51 Recombinase: metabolism
  • Radiotherapy Dosage
  • Retrospective Studies
  • Survival Rate
  • Tissue Array Analysis

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  • Pierre Tennstedt

  • Robert Fresow

  • Ronald Simon

  • Andreas Marx

  • Luigi Terracciano

  • Cordula Petersen

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