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BAX Expression in Hodgkin and Reed-Sternberg Cells of Hodgkin’s Disease

Correlation with Clinical Outcome¹

Departments of Lymphoma-Myeloma [G. Z. R., F. C., A. H. S.], Hematopathology [G. Z. R., L. J. M.], and Molecular Pathology [T. J. M.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Departments of Medical Oncology [S. V., V. B., A. M. G., G. B.] and Pathology [R. G.], Istituto Nazionale Tumori 20133, Milan, Italy; Departments of Hematology [G. N., G. P.] and Pathology [M. C.], University of Verona, 37134 Verona, Italy; and First Department of Internal Medicine [T. P. V., G. A. P.] and Laboratory of Histology and Embryology [C. K.], National and Kapodistrian University of Athens, Athens 11510, Greece

Purpose: 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.

Design: 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.

Conclusion: BAX is often expressed by HRS cells in HD and does not correlate with FFS.

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