1. The prognostic relevance of apoptosis-related proteins in classical Hodgkin's lymphomas.
- Author
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Vassallo J, Metze K, Traina F, de Souza CA, and Lorand-Metze I
- Subjects
- Adolescent, Adult, Aged, Biomarkers, Epstein-Barr Virus Infections metabolism, Female, Hodgkin Disease mortality, Hodgkin Disease pathology, Hodgkin Disease virology, Humans, Life Tables, Male, Middle Aged, Myeloid Cell Leukemia Sequence 1 Protein, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins analysis, RNA, Viral analysis, Retrospective Studies, Survival Analysis, Tumor Virus Infections metabolism, Viral Matrix Proteins analysis, bcl-2-Associated X Protein, bcl-X Protein, fas Receptor analysis, Apoptosis, Hodgkin Disease metabolism, Lewis X Antigen analysis, Neoplasm Proteins analysis, Proto-Oncogene Proteins c-bcl-2 analysis
- Abstract
Neoplastic cells in classical Hodgkin's lymphomas (cHL) seem to correspond to defective germinal center B-cells, which escape from apoptosis. Epstein-Barr virus (EBV) may be implicated in this protective mechanism. The aim of the present study was to determine the expression of apoptosis-related proteins in cHL among adult patients and correlate them with EBV expression, clinical findings and survival. EBV was detected by in situ hybridization (Epstein-Barr Encoded RNA, EBER, probe). Immunohistochemistry was used on paraffin sections to detect LMP-1/EBV, CD15 and the apoptosis-related proteins (bcl-2, bax, bcl-X, mcl-1 and CD95). Seventy-eight patients seen at our Institution were studied: 36 male and 42 female. Median age was 31 years (15-75 years). Histological types of cHL were: 61 nodular sclerosis (47 NS1 and 14 NS2), 15 mixed cellularity (MC), 1 lymphocyte depletion and 1 unclassified. In 50 cases there was EBV expression (64%). At least one apoptosis-associated protein was expressed in 92% and CD15 in 57.7% of the cases. In the univariate analysis, the following variables were related to a better overall survival: expression of CD15 (p = 0.023), expression of mcl-1 protein (p = 0.029), expression of bcl-2 protein (p = 0.028, only in a Cox model after stratification for histology) and expression of LMP-1 (p = 0.042). EBV expression presented a borderline inverse correlation with bcl-2. A prognostic index (PI) developed in the present study revealed that simultaneous expression of bcl-2, mcl-1 and LMP-1 was significant and independently correlated with an excellent survival.
- Published
- 2003
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