EXPRESSION OF P53 PREDICTS TREATMENT FAILURE IN AGGRESSIVE NON-HODGKINS-LYMPHOMAS

Approximately 50% of patients with aggressive non-Hodgkin's lymphomas (NHL) achieve a complete remission (CR) and cure with combination chem otherapy. The International index is a useful clinical measure that pr edicts 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 aggress ive NHL. A retrospective study was carried out on 50 patients with agg ressive NHL who were treated with CHOP chemotherapy. Treatment outcome was correlated with the expression of p53 in the lymphoma, as measure d by routine immunohistochemistry using the monoclonal antibody Do-7. Forty percent of the lymphomas had >5% of the cells staining positivel y for p53 and this finding correlated significantly with response to t reatment. 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 m edian time of 6 months, whereas 26% of the p53 negative group relapsed with the time to relapse being >22 months. The overall survival of th e p53 positive group (17 months) was significantly shorter than that o f p53 negative group (>24 months). These results suggest that the immu nohistochemical assessment of p53 is a simple and important prognostic measure for patients with aggressive NHL who are treated with CHOP ch emotherapy.