The prognostic relevance of apoptosis-related proteins in classical Hodgkin's lymphomas.
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.
Vassallo
José
J
Department of Anatomic Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), PO Box 6111, 13081-970 Campinas, São Paulo, Brazil. glaujv@fcm.unicamp.br
Metze
Konradin
K
Traina
Fabíola
F
de Souza
Cármino A
CA
Lorand-Metze
Irene
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers; D020031:Epstein-Barr Virus Infections / Q000378:metabolism; D005260:Female; D006689:Hodgkin Disease / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology; D006801:Humans; D016256:Lewis X Antigen / Q000032:analysis*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D014412:Tumor Virus Infections / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000032:analysis; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000032:analysis
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D015415:Biomarkers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D016256:Lewis X Antigen; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor