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 poo r outcome in various malignancies. It has been suggested that immunohistoch emical analysis of p53 and p21(Waf1), a downstream target, can be used to s creen for p53 gene mutations. We determined the value of immunohistochemica l screening for p53 gene mutations as a prognostic marker in a population-b ased 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(Wa f1) expression in 34 lymphomas, we established an immunophenotype (Delta p5 3) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry and w as correlated with clinical parameters. Delta p53 showed 100% concordance w ith p53 gene mutation and was detected in 42 cases (21%). Multivariate anal ysis of advanced stage lymphomas showed that Delta p53 was independently as sociated with treatment failure (relative risk, 3.8; P = 0.001), Delta p53 predicted poor survival when analyzing all patients (P = 0.0001), as well a s B-cell (P 0.04) and T-cell NHL (P = 0.000002), In multivariate analysis, Delta p53 (relative risk, 2.2; P = 0.001) maintained prognostic significanc e. The impact on prognosis of Delta p53 was highly significant in the low-i ntermediate-risk group (P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 Delta p53 patients died w ithin 1 year, whereas the median survival of the 28 non-Delta p53 patients was 36 months. These results suggest that immunohistochemically assessed p5 3 status may predict treatment response and outcome in B- and T-cell NHL pa tients.