Expression of bcl-2 in classical Hodgkin's lymphoma: an independent predictor of poor outcome.
OBJECTIVE
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.


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 > or = 45 years, stage III or IV, and IPS > or = 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 > or = 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).


CONCLUSIONS
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.
Sup
Stephen J
SJ
Department of Clinical Pathology, L-11, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH, USA.
Alemañy
Carlos A
CA
Pohlman
Brad
B
Elson
Paul
P
Malhi
Serena
S
Thakkar
Snehal
S
Steinle
Roxanne
R
Hsi
Eric D
ED
D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53