Aberrant P53 expression lacks prognostic or predictive significance in colorectal cancer: results from the VICTOR trial.
OBJECTIVE
Biomarkers with prognostic and predictive value can help stratify patients with colorectal cancer (CRC) into appropriate treatment groups. We sought to evaluate the clinical utility of P53 protein expression as a biomarker in VICTOR, a large phase III trial of rofecoxib in stage II and III CRC.


METHODS
Tissue micro arrays were constructed from 884 tumors and the expression of P53 was examined by immunohistochemistry. Tumors were dichotomised as either P53-positive (nuclear expression in >10% of cells or the 'absent' pattern, both representing TP53 mutation) or P53-negative (nuclear expression in <10% of cells).


RESULTS
Aberrant P53 expression was found in 65% (482/740) of patients. It was associated with distal location (p<0.001) and stage III disease (p<0.001). No effect was observed on disease-free or overall survival, and there was no interaction with chemotherapy or radiotherapy.


CONCLUSIONS
Analysis of P53 expression in the patients recruited to the VICTOR trial confirmed that P53 expression is associated with site and stage of CRC. However, independently, this biomarker has neither prognostic nor predictive utility in this cohort of patients.
Department of Oncology, Old Road Campus Research Building, University of Oxford, Oxford, U.K.
Megan J
MJ
McGregor
Queen's Medical Centre, School of Medicine, University of Nottingham, Nottingham, U.K.
Wakkas
W
Fadhil
Centre for Statistics in Medicine, University of Oxford, Oxford, U.K.
Rose
R
Wharton
Department of Oncology, Old Road Campus Research Building, University of Oxford, Oxford, U.K.
Yoko
Y
Yanagisawa
Department of Oncology, Old Road Campus Research Building, University of Oxford, Oxford, U.K.
Michael
M
Presz
AstraZeneca Oncology Innovative Medicines, Mereside, Macclesfield, Cheshire, U.K.
Alison
A
Pritchard
AstraZeneca Oncology Innovative Medicines, Mereside, Macclesfield, Cheshire, U.K.
Chris
C
Womack
Centre for Statistics in Medicine, University of Oxford, Oxford, U.K.
Susan
S
Dutton
Department of Oncology, Old Road Campus Research Building, University of Oxford, Oxford, U.K.
Rachel S
RS
Kerr
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, U.K.
David J
DJ
Kerr
Department of Oncology, Old Road Campus Research Building, University of Oxford, Oxford, U.K.
Elaine C
EC
Johnstone
Queen's Medical Centre, School of Medicine, University of Nottingham, Nottingham, U.K. mohammad.ilyas@nottingham.ac.uk.
Mohammad
M
Ilyas
D015415:Biomarkers; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D007783:Lactones / Q000627:therapeutic use*; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D013450:Sulfones / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D015415:Biomarkers; D007783:Lactones; D013450:Sulfones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C116926:rofecoxib
Colorectal cancer; P53; biomarkers; immunohistochemistry; prognosis