Expression of P53 Predicts Treatment Failure in Aggressive Non-Hodgkin's Lymphomas

Abstract

Approximately 50% of patients with aggressive non-Hodgkin's lymphomas (NHL) achieve a complete remission (CR) and cure with combination chemotherapy. The International Index is a useful clinical measure that predicts the patients' tolerance of therapy and likelihood of achieving CR, but it is not a direct measure of chemosensitivity. In this study we have investigated the predictive value of the tumor suppressor gene, p53, as a biological marker for response to treatment in the aggressive NHL. A retrospective study was carried out on 50 patients with aggressive NHL who were treated with CHOP chemotherapy. Treatment outcome was correlated with the expression of p53 in the lymphoma, as measured by routine immunohistochemistry using the monoclonal antibody Do-7. Forty percent of the lymphomas had >5% of the cells staining positively for p53 and this finding correlated significantly with response to treatment. Fifty percent of patients with p53 positive tumors achieved a CR versus 77% of patients with p53 negative tumors. In addition, the relapse rate and time to relapse were significantly different in the two groups. In the p53 positive group, 60% of patients relapsed in a median time of 6 months, whereas 26% of the p53 negative group relapsed with the time to relapse being >22 months. The overall survival of the p53 positive group (17 months) was significantly shorter than that of p53 negative group (>24 months). These results suggest that the immunohistochemical assessment of p53 is a simple and important prognostic measure for patients with aggressive NHL who are treated with CHOP chemotherapy.

Apoptosis-Regulating Proteins and Prognosis in Diffuse Large B Cell Non-Hodgkin’s Lymphomas

“…Overexpression of p53 protein is usually associated with a loss of p53 gene function [19], favoring drug resistance and a worse prognosis. Corroborating our results, Navaratnam et al [21]showed that patients with p53-positive tumors had a low rate of CR and a reduced overall survival. Abnormalities of p53 gene (mutation or overexpression) were associated with drug resistance and a shorter median PFS and OS (11.7 vs 21.5 months, p = 0.038) [16].…”

“…Overexpression of p53 is frequently associated with an abnormal protein function [19]and has a prognostic value [16, 20, 21, 22, 23]. …”

Prognostic Significance of P53, Bcl-2, and Fas Expression in Patients with Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

“…P53 protein expression differs with respect to histological subtypes in gastrointestinal lymphomas (17%-20%), whereas this rate ranges between 60% and 85% in high-grade lymphomas. Different studies have identified that P53 protein expression is an important prognostic factor that affects the treatment response and overall survival in patients with aggressive NHL (12,13). In our study, we found P53 expression in 61.5% of the patients with primary gastrointestinal DLBCL.…”

p53 abnormalities in splenic lymphoma with villous lymphocytes

“…It has been suggested that the presence of p53 mutations influences the pathologic grade 10 but not the clinical behavior. Several studies showed a strong correlation between clinical progression and occurrence of p53 mutations, [11][12][13][14][15][16][17] but others did not. 18,19 Our aim was to establish the frequency and importance of abnormalities in p53 in SLVL.…”