Clinical Significance of bcl-2 and p53 protein Expression in Patients with Malignant Lymphoma

Hong, Sul Yoo; Hong, Dae Sik; Kim, Sook Ja; Park, Sung Kyu; Lee, Gyu Taeg; Kim, Dae Joong; Won, Jong Ho; Suh, Won Suk; Baick, Seung Ho; Park, Hee Sook

Abstract

BACKGROUND
Overexpression of bcl-2 protein is observed both in follicular lymphoma, in which bcl-2 has usually undergone a translocation t (14;18). The experimental findings that transfection of bcl-2 in to murine lymphoid cells confers resistance to nitrogen mustard and camptothecin by inhibiting apoptosis suggests that bcl-2 overexpression may confer clinical drug resistance in lymphomas. In contrast to bcl-2, p53 arrests cells exposed to DNA-damaging agents in G1 to allow DNA repair or if essential repairs are not possible, promotes apoptosis. Experimentally, loss of p53 function produces cellular resistance to alkylating and topoisomerase-II drug classes, suggesting that loss of p53 function in lymphomas may cause drug resistance. These observations led to the hypothesis that bcl-2 and p53 play a role in the development of drug resistance in lymphoma. Although several studies assessed the association between bcl-2 expression and disease-free survival, they reached conflicting conclusions.
METHODS
We analyzed tumor tissue from 42 patients with advanced NHL for p53 and bcl-2 expression and correlation with multiple clinical characteristics, response to therapy and overall survival. Among 42 tumors, 8 (19.0%) tumors had bcl-2 expression and 19 (45.2%) had a p53 overexpression.
RESULTS
A significant correlation was found between bcl-2 expression and poor performance, advanced stage (stage III and IV) at diagnosis, and bone marrow involvement in a univariate analysis (P<0.05). A multivariate analysis showed that tumors with bcl-2 expression (>50%) were more likely to be poor prognosis than tumors with negative or week expression (<50%) and to have a shorter long-term survival (28.6% vs 75.5%; P<0.05). However, the expression of p53 did not correlate with any clinical characteristics and overall survival was not influenced by p53 protein expression.
CONCLUSION
These results suggest that bcl-2 protein expression in patients with malignant lymphoma appears to be predictive of shorter long-term survival and it might be considered as a strong independent prognostic factor.