Abstract 1983: TP53 mutations in hepatocellular carcinoma: Association with survival and stem cell-like gene expression traits

Abstract

Abstract PURPOSE Mutations of TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic value of TP53 mutations in hepatocellular carcinoma (HCC) is still unclear, largely because of the enormous heterogeneity in the geographic and etiological backgrounds of the HCC patients. Here, we analyzed the prognostic values of TP53 mutations. Gene expression profiling analysis was performed to evaluate the effect of TP53 mutations at the molecular level. PATIENTS AND METHODS TP53 mutations were investigated in a total of 409 HCC patients including Chinese (n=336) and Caucasian (n=73) patients using direct sequencing method. RESULTS A total of 125 TP53 mutations were found in Chinese HCC patients (37.2 %). HCC patients harboring TP53 mutations showed shorter overall survival compared to patients with wild-type TP53 (Hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.37-2.52; P<0.001). The hotspot mutations at R249S and V157F were significantly associated with worse prognosis in both univariate (HR, 2.11; 95% CI, 1.51-2.94; P<0.001) and multivariate analyses (HR, 1.79; 95% CI, 1.29-2.51; P<0.001). In addition, gene expression profile analysis revealed the expression of stem cell-like traits in TP53 mutated tumors. This finding was validated in breast and lung cancers with TP53 mutations. CONCLUSION TP53 mutations, particularly hotspot mutations, are associated with poor prognosis in HCC. The acquisition of stem cell-like gene expression traits may contribute to the aggressive behavior of the TP53 mutated tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1983.