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Carcinogenesis Advance Access published online on January 27, 2007
Carcinogenesis, doi:10.1093/carcin/bgm012
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

David G. Molleví, PhD1, Teresa Serrano, MD, PhD2, Mireia M. Ginestà, PhD1, Joan Valls, BD3, Jaume Torras, MD, PhD4, Matilde Navarro, MD5, Emilio Ramos, MD, PhD4, Josep Ramón Germà, MD, PhD5, Eduardo Jaurrieta, MD, PhD4, Víctor Moreno, MD, PhD3, Joan Figueras, MD, PhD6, Gabriel Capellà, MD, PhD1 and Alberto Villanueva, PhD1

1 Laboratory of Translational Research, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
2 Department of Pathology, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
3 Department of Cancer Epidemiology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain and Laboratori de Bioestadística i Epidemiologia, Facultat de Medicina, Universitat Autònoma de Barcelona
4 Hepatobilliary Surgery Unit, Department of Surgery, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
5 Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
6 Hepatobilliary Surgery Unit, Department of Surgery, Hospital Josep Trueta, Girona, Spain

Correspondence should be addressed to: Alberto Villanueva PhD; Laboratory of Translational Research. Institut Català d'Oncologia-IDIBELL. Hospital Duran i Reynals. L'Hospitalet de Llobregat, 08907 Barcelona, Spain; Telephone: 34-93 260 79 52; Fax: 34-93 260 74 66; e-mail: avillanueva{at}iconcologia.net

The aim of this study was to analyze the prognostic value of TP53 mutations in a consecutive series of patients with hepatic metastases from colorectal cancer undergoing surgical resection.

91 patients with liver metastases from colorectal carcinoma were included. Mutational analysis of TP53, exons 4 to 10, was performed by SSCP (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 out 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 % (n=22) were protein-truncating mutations. TP53 status associated with multiple (≥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% 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 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 hepatic metastases.

Key Words: Colorectal hepatic metastases • TP53 mutations • survival prognostic • P53 and P21 immunohistochemical • postoperative chemotherapy treatment


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