BAX expression in Hodgkin and Reed-Sternberg cells of Hodgkin's disease: correlation with clinical outcome.
OBJECTIVE
BAX, a proapoptotic member of the BCL-2 family of proteins, has been detected in Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD), but its clinical significance is unknown. Therefore, we correlated BAX expression with presenting features and clinical outcome in untreated patients with HD.


METHODS
Patients with biopsy-proven HD were eligible if they were untreated previously and if pretreatment paraffin-embedded tumor tissue was available. BAX was detected by immunohistochemistry without knowledge of clinical features or outcome. A tumor was considered as positive if any number of HRS cells expressed BAX, but other cutoffs of BAX expression were examined for analysis of clinical outcome.


RESULTS
We identified 260 patients with HD. The median age was 31 years, and 55% were male. HRS cells expressed BAX in 181 of 195 (93%) nodular sclerosis, 47 of 48 (98%) mixed cellularity, 1 case of lymphocyte depletion, all 6 unclassified classical HD, and all 10 lymphocyte predominance tumors. Using a cutoff of 50% positive HRS cells for BAX expression, the 5-year failure-free survival (FFS) for patients with high versus low BAX expression was 83 versus 93%, respectively (P = 0.19 by Log-rank) for 116 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens; it was 78 versus 79%, respectively, for 79 patients treated with mitoxantrone, vincristine, vinblastine, and prednisone and radiotherapy (P = 0.45 by Log-rank); it was 71 versus 81%, respectively, for 26 patients treated with nitrogen mustard, vincristine, prednisone, and procarbazine (P = 0.6 by Log-rank); and it was 72 versus 82% for 29 patients treated only with radiotherapy (P = 0.57 by Log-rank). The 5-year FFS was not statistically different when we used cutoffs of 20, 30, and 75% for BAX expression.


CONCLUSIONS
BAX is often expressed by HRS cells in HD and does not correlate with FFS.
Rassidakis
George Z
GZ
Department of Lymphoma-Myeloma, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. gzrassidakis@mail.mdanderson.org
Medeiros
L Jeffrey
LJ
McDonnell
Timothy J
TJ
Viviani
Simonetta
S
Bonfante
Valeria
V
Nadali
Gianpaolo
G
Vassilakopoulos
Theodoros P
TP
Giardini
Roberto
R
Chilosi
Marco
M
Kittas
Christos
C
Gianni
Alessandro M
AM
Bonadonna
Gianni
G
Pizzolo
Giovanni
G
Pangalis
Gerassimos A
GA
Cabanillas
Fernando
F
Sarris
Andreas H
AH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein