Influence of biologic markers on the outcome of Hodgkin's lymphoma: a study by the Spanish Hodgkin's Lymphoma Study Group.
OBJECTIVE
Current therapies fail to cure a significant proportion of patients with Hodgkin's lymphoma (HL). Predictive systems for stratification of the disease and selection of treatment based on sets of clinical variables, such as the international prognostic score (IPS), are of relatively small practical value. The predictive use of biologic parameters has so far provided limited and inconsistent results. Here we explore the influence of a set of molecular markers on the outcome of HL.


METHODS
Forty molecular markers involved in B-cell differentiation and activation, signal transduction, cell cycle, and apoptosis control were analyzed in 259 classic HL patient cases by using tissue microarrays. Univariate analysis was performed to evaluate the influence of markers on favorable outcome (complete remission of > 12 months). Significant variables were included in a multivariate logistic regression analysis, and the probability of favorable outcome was estimated.


RESULTS
Univariate analysis revealed four molecular markers that predicted outcome, and the multivariate analysis showed p53, Bcl-X(L), and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) to have independent significance. The combination of these factors determined two groups of patients (group I, zero to one factor; group II, two to three factors) with a probability of a favorable outcome of.948 and.687, respectively. A multivariate Cox's model shows that these biologic risk groups have special predictive power in low-IPS patients.


CONCLUSIONS
The data from this exploratory study suggest that the accumulation of molecular events seems to influence the outcome of HL, particularly in the low-IPS group.
Montalbán
Carlos
C
Medicina Interna, Hematología and Unidad de Bioestradistica Clínica, Hospital Ramón y Cajal, Madrid, Spain.
García
Juan F
JF
Abraira
Víctor
V
González-Camacho
Leocricia
L
Morente
Manuel M
MM
Bello
Jose L
JL
Conde
Eulogio
E
Cruz
Miguel A
MA
García-Sanz
Ramón
R
García-Laraña
José
J
Grande
Carlos
C
Llanos
Marta
M
Martínez
Rafael
R
Flores
Eduardo
E
Méndez
Miguel
M
Ponderós
Concepción
C
Rayón
Concepción
C
Sánchez-Godoy
Pedro
P
Zamora
Javier
J
Piris
Miguel A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002453:Cell Cycle; D002454:Cell Differentiation; D002648:Child; D005260:Female; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
D014408:Biomarkers, Tumor