The Prognostic Relevance of Apoptosis-related Proteins in Classical Hodgkin's Lymphomas

• Published in: Leukemia & lymphoma 2003-01, Vol.44 (3), p.483-488
• Main Authors: Vassallo, José, Metze, Konradin, Traina, Fabíola, A. de Souza, Cármino, Lorand-Metze, Irene
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Apoptosis; Apoptosis, Immunohistochemistry; bcl-2-Associated X Protein; bcl-X Protein; Biomarkers; Epstein-Barr Virus; Epstein-Barr Virus Infections - metabolism; fas Receptor - analysis; Female; Hodgkin Disease - metabolism; Hodgkin Disease - mortality; Hodgkin Disease - pathology; Hodgkin Disease - virology; Hodgkin's Lymphoma; Humans; In Situ Hybridization; Lewis X Antigen - analysis; Life Tables; Male; Middle Aged; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins - analysis; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins c-bcl-2 - analysis; Retrospective Studies; RNA, Viral - analysis; Survival Analysis; Tumor Virus Infections - metabolism; Viral Matrix Proteins - analysis
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/1042819021000037958

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.