Originally published as JCO Early Release 10.1200/JCO.2005.04.358 on April 4 2005

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Expression of bcl-2 in Classical Hodgkin's Lymphoma: An Independent Predictor of Poor Outcome

From the Department of Clinical Pathology, and Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH

Address reprint requests Eric D. Hsi, M.D., Department of Clinical Pathology, L-11, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH; e-mail: hsie{at}ccf.org

PURPOSE: Although most classical Hodgkin's lymphoma (CHL) patients are cured, a significant minority fails primary therapy and may die as a result of their disease. Age, stage, and other basic clinical and laboratory parameters, which comprise the International Prognostic Score (IPS), are used at diagnosis to predict outcome. To date, there is no consensus on biologic markers that add value to these parameters.

PATIENTS AND METHODS: We evaluated 107 CHL patients for bcl-2, p53, and p21 expression by immunohistochemistry using tissue microarrays and correlated the results with outcome. The median follow-up of the 79 surviving patients was 6.8 years.

RESULTS: Univariate analysis showed that age 45 years, stage III or IV, and IPS 3 were associated with a poor failure-free survival (FFS) and overall survival (OS). bcl-2 was expressed in 26% of patients and was associated with poor FFS and a trend for OS. p53 expression in combination with lack of p21 expression was not associated with outcome. Multivariate analysis showed that three factors were independently associated with both FFS and OS: age 45 years, stage III or IV, and bcl-2 expression. Using these three parameters, a scoring system was devised that stratified patients into three risk groups (with zero, one, or two to three of these risk factors) and a progressively worse FFS and OS (P < .001).

CONCLUSION: Expression of bcl-2 in CHL is a useful, independent prognostic marker and can be used in association with clinical parameters to identify newly diagnosed patients with a good, intermediate, or poor prognosis.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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