RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma

TY - JOUR

T1 - RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma

AU - Tennstedt, Pierre

AU - Fresow, Robert

AU - Simon, Ronald

AU - Marx, Andreas

AU - Terracciano, Luigi

AU - Petersen, Cordula

AU - Sauter, Guido

AU - Dikomey, Ekkehard

AU - Borgmann, Kerstin

N1 - Copyright © 2012 UICC.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - 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.

AB - 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.

KW - Adenocarcinoma

KW - Aged

KW - Colorectal Neoplasms

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Immunoenzyme Techniques

KW - Male

KW - Neoplasm Grading

KW - Neoplasm Staging

KW - Prognosis

KW - Rad51 Recombinase

KW - Radiotherapy Dosage

KW - Retrospective Studies

KW - Survival Rate

KW - Tissue Array Analysis

KW - Tumor Markers, Biological

U2 - 10.1002/ijc.27907

DO - 10.1002/ijc.27907

M3 - SCORING: Journal article

C2 - 23065657

VL - 132

SP - 2118

EP - 2126

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 9

ER -