Disrupted p53 Function as Predictor of Treatment Failure and Poor Prognosis in B- and T-Cell Non-Hodgkin’s Lymphoma

Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical analysis of p53 and p21 Waf1 , a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin’s lymphomas (NHLs). On the basis of p53 gene mutation status and immunohistochemically detected p53 and p21 Waf1 expression in 34 lymphomas, we established an immunophenotype (Δp53) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry and was correlated with clinical parameters. Δp53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis of advanced stage lymphomas showed that Δp53 was independently associated with treatment failure (relative risk, 3.8; P = 0.001). Δp53 predicted poor survival when analyzing all patients ( P = 0.0001), as well as B-cell ( P = 0.04) and T-cell NHL ( P = 0.000002). In multivariate analysis, Δp53 (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of Δp53 was highly significant in the low-intermediate-risk group ( P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 Δp53 patients died within 1 year, whereas the median survival of the 28 non-Δp53 patients was 36 months. These results suggest that immunohistochemically assessed p53 status may predict treatment response and outcome in B- and T-cell NHL patients.