The aim of this study was to analyze the prognostic value of TP53 mutations 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 of TP53, 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 of TP53 mutations and
chemotherapy treatment. Forty-six of 91 (50.05%)
metastases showed mutations in TP53, 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. TP53 status associated with multiple (> or =3)
metastases (65.6%, P = 0.033), advanced primary
tumor Dukes' stage (P = 0.011) and younger age (<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 > or =3
metastases and TP53 mutation identified a subset of patients with very poor prognosis (P = 0.009). P53 and P21
protein immunostaining did not show correlation with survival. TP53 mutational status seems to be an important prognostic factor in patients undergoing surgical resection of
colorectal cancer HMs.