RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma.

ABSTRACT

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 ß-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.