Clinical Significance of bcl-2 and p53 protein Expression in Patients with Malignant Lymphoma.
- Author:
Sul Yoo HONG
1
;
Dae Sik HONG
;
Sook Ja KIM
;
Sung Kyu PARK
;
Gyu Taeg LEE
;
Dae Joong KIM
;
Jong Ho WON
;
Won Suk SUH
;
Seung Ho BAICK
;
Hee Sook PARK
Author Information
1. Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Non-Hodgkin's Lymphoma;
bcl-2 protein;
p53 protein
- MeSH:
Apoptosis;
Bone Marrow;
Camptothecin;
Diagnosis;
Disease-Free Survival;
DNA Repair;
Drug Resistance;
Humans;
Lymphocytes;
Lymphoma*;
Lymphoma, Follicular;
Lymphoma, Non-Hodgkin;
Mechlorethamine;
Multivariate Analysis;
Prognosis;
Transfection
- From:Korean Journal of Hematology
1999;34(1):43-51
- CountryRepublic of Korea
- Language:Korean
-
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.
