Negative p53 Expression Confers Worse Prognosis in Patients With Resected Pancreatic Ductal Adenocarcinoma: Research Focused on Reinterpretation of Immunohistochemical Staining.

ABSTRACT

OBJECTIVE: The aim of the study is to reinterpret the prognostic prediction of p53 expression categories in pancreatic ductal adenocarcinoma with exploration of the relationship between TP53 mutation genotype and p53 expression pattern. METHODS: Data were retrospectively collected from consecutive patients who underwent primary pancreatic resection. Complete loss of function of TP53 is defined as nonsense and frameshift mutations. A tissue microarray was used to evaluate p53 expression by immunohistochemistry and was categorized as regulated, high, or negative. RESULTS: The κ coefficient for agreement between p53 expression and TP53 was 0.761. Cox regression analyses revealed that p53 expression (high vs regulated hazard ratio [HR], 2.225; P < 0.001; negative vs regulated HR, 2.788; P < 0.001), tumor-node-metastasis stage (II vs I HR, 3.471; P < 0.001; III vs I HR, 6.834; P < 0.001), and tumor grade (G3/4 vs G1/2 HR, 1.958; P < 0.001) were independent prognostic factors in developing cohort and validation cohort. In subgroups of stage I, II, and III, compared with regulated expression, the patients with negative expression had a worse prognosis in both cohorts (P < 0.05). CONCLUSIONS: Our findings indicate that 3-tier p53 expression in resectable pancreatic ductal adenocarcinoma provided independent prognostic information complementary to the tumor-node-metastasis staging system and facilitated patient stratification for personalized therapy.