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.
Sohn SK
，Jung JT
，Kim DH
，Kim JG
，Kwak EK
，Park Ti
，Shin DG
，Sohn KR
，Lee KB
... -
《AMERICAN JOURNAL OF HEMATOLOGY》
Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2.
We investigated the association of the apoptosis related proteins Bcl-2, Bcl-x, Bax and Bak, p53, the adhesion molecule E-cadherin, the receptor proteins epidermal growth factor receptor and c-erbB-2, and the proliferation markers proliferating cell nuclear antigen and Ki-67 with the clinical outcome of bilharzial related transitional cell carcinoma and squamous cell carcinoma.
Cystectomy specimens from 109 patients with organ confined, muscle invasive stage, pT2pN0M0, bilharziall positive bladder cancer were examined, including 60 with squamous cell carcinoma and 49 with transitional cell carcinoma. Immunohistochemical results were correlated with tumor progression.
In squamous cell carcinoma but not in transitional cell carcinoma the loss of epidermal growth factor receptor, Bax and Bak was significantly associated with higher histological grade (p = 0.02, 0.006 and 0.01, respectively). On univariate analysis patients with transitional cell carcinoma had a poorer prognosis than those with squamous cell carcinoma. p53 Over expression and the loss of Bak positivity were associated with shortened progression-free survival in transitional cell carcinoma (p = 0.006 and 0.04, respectively), and squamous cell carcinoma (p = 0.00001 and 0.04, respectively). In squamous cell carcinoma high tumor grade (p = 0.02) and in transitional cell carcinoma high labeling indexes for MIB-1, Bcl-x expression and c-erbB-2 positivity (p = 0.03, 0.02 and 0.04, respectively) were associated with a poorer prognosis. On multivariate analysis p53 emerged as a significant prognostic factor for each condition. Additional independent prognostic factors were proliferating cell nuclear antigen for squamous cell carcinoma, and MIB-1, Bcl-x and Bax for transitional cell carcinoma.
Bilharzial related transitional cell carcinoma and squamous cell carcinoma of the bladder differ in interims of protein expression and prognosis. Independent prognostic factors were p53, MIB-1, Bcl-x, and Bax in the former disease, and p53 and proliferating cell nuclear antigen in the latter disease.
Haitel A
，Posch B
，El-Baz M
，Mokhtar AA
，Susani M
，Ghoneim MA
，Marberger M
... -
《JOURNAL OF UROLOGY》
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