RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma
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RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma. / Tennstedt, Pierre; Fresow, Robert; Simon, Ronald; Marx, Andreas; Terracciano, Luigi; Petersen, Cordula; Sauter, Guido; Dikomey, Ekkehard; Borgmann, Kerstin.
In: INT J CANCER, Vol. 132, No. 9, 01.05.2013, p. 2118-26.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -