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The aim of this study was to analyze the prognostic value ofTP53mutations in a consecutive series of patients with hepatic metastases (HMs) from colorectal cancer undergoing surgical resection. Ninety-one patients with liver metastases from colorectal carcinoma were included. Mutational analysis ofTP53, exons 4–10, was performed by single-strand conformation polymorphism and sequencing. P53 and P21 protein immunostaining was assessed. Multivariate Cox models were adjusted for gender, number of metastasis, resection margin, presence ofTP53mutations and chemotherapy treatment. Forty-six of 91 (50.05%) metastases showed mutations inTP53, observed mainly in exons 5–8, although 14.3% (n= 13) were located in exons 9 and 10. Forty percent (n= 22) were protein-truncating mutations.TP53status associated with multiple (≥3) metastases (65.6%,P= 0.033), advanced primary tumor Dukes' stage (P= 0.011) and younger age (&lt;57 years old,P= 0.03). Presence of mutation associated with poor prognosis in univariate (P= 0.017) and multivariate Cox model [hazard ratio (HR) = 1.80, 95% confidence interval (CI) = 1.07–3.06,P= 0.028]. Prognostic value was maintained in patients undergoing radical resection (R0 series,n= 79,P= 0.014). Mutation associated with a worse outcome in chemotherapy-treated patients (HR = 2.54, 95% CI = 1.12–5.75,P= 0.026). The combination of ≥3 metastases andTP53mutation identified a subset of patients with very poor prognosis (P= 0.009). P53 and P21 protein immunostaining did not show correlation with survival.TP53mutational status seems to be an important prognostic factor in patients undergoing surgical resection of colorectal cancer HMs.

Mutations in TP53 are a prognostic factor in colorectal hepatic metastases undergoing surgical resection