Carcinogenesis Advance Access originally published online on January 27, 2007
Carcinogenesis 2007 28(6):1241-1246; doi:10.1093/carcin/bgm012
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Mutations in TP53 are a prognostic factor in colorectal hepatic metastases undergoing surgical resection
Laboratory of Translational Research, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, 08907 Barcelona, Spain
1 Department of Pathology, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, 08907 Barcelona, Spain
2 Department of Cancer Epidemiology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, 08907 Barcelona, Spain and Laboratori de Bioestadística i Epidemiologia, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
3 Hepatobilliary Surgery Unit, Department of Surgery, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
4 Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, 08907 Barcelona, Spain
5 Hepatobilliary Surgery Unit, Department of Surgery, Hospital Josep Trueta, 17007 Girona, Spain
* To whom correspondence should be addressed. Tel: +34 93 260 79 52; Fax: +34 93 260 74 66; Email: 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 (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 (
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 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.
Abbreviations: CI, confidence interval; CRC, colorectal carcinoma; DFS, disease-free survival; 5-FU, 5-fluorouracil; HM, hepatic metastasis; HR, hazard ratio; OS, overall survival; PCR, polymerase chain reaction; wt, wild type
Received August 18, 2006; revised December 28, 2006; accepted January 16, 2007.