Prognostic significance of bcl-2, bax, and p53 expression in diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLCL) exhibits heterogeneous clinical features and varies markedly in response to treatment and prognosis. Because apoptosis-related proteins may play an important role in predicting the prognosis of DLCL, the current study investigated the prognostic significance of a high level of bcl-2, bax, and p53 expression in relation to clinical characteristics in patients with DLCL. Paraffin-embedded specimens from 94 patients with de novo DLCL were analyzed immunohistochemically for bcl-2, bax, and p53 gene expression. Cases with a positive immunohistological stain in more than 50% of the tumor cells were considered to have DLCL-positive expression. Patients were treated optimally, i.e., with radiotherapy including brief cycles of CHOP or CHOP-like regimens for patients with stage 1-2A diseases and with at least 6 cycles of CHOP or CHOP-like regimens for stage 2B-4 diseases. The responses to therapy and survival were then analyzed in 94 uniformly staged patients. bcl-2 expression was identified in 24 patients (26.4%), bax expression in 35 patients (37.6 %), and p53 expression in 21 patients (22.6%). bax expression proved to be a statistically significant prognostic factor in predicting the overall survival (OS) (P = 0.0015) and disease-free survival (DFS) (P = 0.0052), regardless of other clinical factors or immunohistological results. There was no significant difference in the OS (P = 0.0682) or DFS (P = 0.088) between the bcl-2-positive (n = 24) and bcl-2-negative (n = 67) groups. However, bcl-2 expression was found to be unfavorably associated with the OS (P = 0.0054) in a confined group with low (n = 51) or low intermediate (n = 22) IPI scores. The expression of p53 exhibited no statistical correlation with the OS or DFS. A multivariate analysis revealed that IPI score, bulky mass, and bax expression were all significantly associated with the DFS or OS. bax and bcl-2 should be considered as independent biologic prognostic parameters in DLCL, thereby aiding in the identification of patient risk groups. As such, bcl-2-positive patients with a low or low intermediate IPI score, or without a high level of bax expression could be candidates for more intensive therapy or alternative therapeutic approaches.
Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea. sksohn@knu.ac.kr
Sang Kyun
SK
Sohn
Jin Tae
JT
Jung
Dong Hwan
DH
Kim
Jong Gwang
JG
Kim
Eun Kyung
EK
Kwak
Tae in
Ti
Park
Dong Gun
DG
Shin
Kyung Rak
KR
Sohn
Kyu Bo
KB
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein