title: Mutations in TP53 are a prognostic factor in colorectal hepatic metastases undergoing surgical resection.
abstract: 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.
authors.affiliation: Laboratory of Translational Research, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: David G
authors.initials: DG
authors.lastname: Molleví
authors.forename: Teresa
authors.initials: T
authors.lastname: Serrano
authors.forename: Mireia M
authors.initials: MM
authors.lastname: Ginestà
authors.forename: Joan
authors.initials: J
authors.lastname: Valls
authors.forename: Jaume
authors.initials: J
authors.lastname: Torras
authors.forename: Matilde
authors.initials: M
authors.lastname: Navarro
authors.forename: Emilio
authors.initials: E
authors.lastname: Ramos
authors.forename: Josep R
authors.initials: JR
authors.lastname: Germà
authors.forename: Eduardo
authors.initials: E
authors.lastname: Jaurrieta
authors.forename: Víctor
authors.initials: V
authors.lastname: Moreno
authors.forename: Joan
authors.initials: J
authors.lastname: Figueras
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellà
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53