Overexpression of TP53 protein is associated with the lack of adjuvant chemotherapy benefit in patients with stage III colorectal cancer
David S Williams, Dmitri Mouradov, Clare Browne, Michelle Palmieri, Meg J Elliott, Rebecca Nightingale, Catherine G Fang, Rita Li, John M Mariadason, Ian Faragher, Ian T Jones, Leonid Churilov, Niall C Tebbutt, Peter Gibbs, Oliver M Sieber
MODERN PATHOLOGY | NATURE PUBLISHING GROUP | Published : 2020
TP53 mutations drive colorectal cancer development, with missense mutations frequently leading to accumulation of abnormal TP53 protein. TP53 alterations have been associated with poor prognosis and chemotherapy resistance, but data remain controversial. Here, we examined the predictive utility of TP53 overexpression in the context of current adjuvant treatment practice for patients with stage III colorectal cancer. A prospective cohort of 264 stage III patients was tested for association of TP53 expression with 5-year disease-free survival, grouped by adjuvant treatment. Findings were validated in an independent retrospective cohort of 274 stage III patients. Overexpression of TP53 protein ..View full abstract
Awarded by Priority-driven Collaborative Cancer Research Scheme
The authors thank the Victorian Cancer BioBank and Biogrid Australia for provision of patient specimens and clinical data. This work was supported by grant #1120882, awarded through the Priority-driven Collaborative Cancer Research Scheme and funded by Cancer Australia (to O.M.S), the Victorian Government' Operational Infrastructure Support Program, a University of Melbourne Department of Pathology Career Development Award (to D.S.W.) and an Austin Medical Research Foundation Project Grant (to D.S.W). OMS (GNT1136119) and JMM (GNT104692) are NHMRC Senior Research Fellows.