TP53 status is an important prognostic marker for patients with hepatic metastases from colorectal carcinoma

Abstract

10092 Background: The aim of this study was to analyze the value of TP53 gene mutations as a prognostic marker to improve the selection of patients candidates to surgery in a consecutive series of liver metastases from colorectal cancer patients. Methods: 91 patients with liver metastases from colorectal carcinoma (CRC) were included. Mutational study of TP53 gene, exons 4 to 10, was assessed both in paraffin-embedded hepatic metastasis and normal liver parenchyma by SSCP (Single Strand Chain Polymorphism) followed by sequencing of abnormal electrophoretic mobility patterns. Immunostaining of P53 and P21 proteins were assessed in the same group of patients. Results: Forty-eight out 91 (50.05%) metastases showed mutation in TP53. Higher incidence of mutations was detected in exons 5–8, although exons 9 and 10 were mutated in 28.26% of metastases. Protein-truncating mutations (nonsense and frameshift) occur in 47.8% of metastasis harboring TP53 mutations. TP53 mutation was associated with poor prognosis in univariate (P=0.0062) and multivariate Cox proportional hazard model (P=0.012) analysis. Prognosis association was maintained in the group of patients undergoing radical resection, named R0 series (n=79; P=0.008). High prevalence of TP53 mutations happen in patients with >3 metastases (65.6%; P=0.034), primary tumors Duke’s C-D stages (57.4%; 63.0%; respectively; p=0.026) and patients with age <57 years at resection. Interestingly, patients with TP53 mutations in their metastases relapsed earlier after the resection of the primary tumor (P=0.026). Postoperative 5-FU-based chemotherapy showed a better survival outcome in patients with wild-type TP53 hepatic metastases (HR: 2.92; 95% CI: 1.32–6.46; P=0.006). Conclusions: TP53 mutational status seems to be an important prognostic factor in patients with hepatic metastases from CRC. No significant financial relationships to disclose.