A TaqMan low-density array to predict outcome in advanced Hodgkin's lymphoma using paraffin-embedded samples.
OBJECTIVE
Despite major advances in the treatment of classic Hodgkin's lymphoma (cHL), approximately 30% of patients in advanced stages may eventually die as result of the disease, and current methods to predict prognosis are rather unreliable. Thus, the application of robust techniques for the identification of biomarkers associated with treatment response is essential if new predictive tools are to be developed.


METHODS
We used gene expression data from advanced cHL patients to identify transcriptional patterns from the tumoral cells and their nonneoplastic microenvironment, associated with lack of maintained treatment response. Gene-Set Enrichment Analysis was used to identify functional pathways associated with unfavorable outcome that were significantly enriched in either the Hodgkin's and Reed-Sternberg cells (regulation of the G2-M checkpoint, chaperones, histone modification, and signaling pathways) or the reactive cell microenvironment (mainly represented by specific T-cell populations and macrophage activation markers).


RESULTS
To explore the pathways identified previously, we used a series of 52 formalin-fixed paraffin-embedded advanced cHL samples and designed a real-time PCR-based low-density array that included the most relevant genes. A large majority of the samples (82.7%) and all selected genes were analyzed successfully with this approach.


CONCLUSIONS
The results of this assay can be combined in a single risk score integrating these biological pathways associated with treatment response and eventually used in a larger series to develop a new molecular outcome predictor for advanced cHL.
Sánchez-Espiridión
Beatriz
B
The Lymphoma Group and Tumour Bank Network, Department of Molecular Pathology, Spanish National Cancer Centre, Madrid, Spain.
Sánchez-Aguilera
Abel
A
Montalbán
Carlos
C
Martin
Carmen
C
Martinez
Rafael
R
González-Carrero
Joaquín
J
Poderos
Concepción
C
Bellas
Carmen
C
Fresno
Manuel F
MF
Morante
Cesar
C
Mestre
Maria J
MJ
Mendez
Miguel
M
Mazorra
Francisco
F
Conde
Eulogio
E
Castaño
Angel
A
Sánchez-Godoy
Pedro
P
Tomas
José F
JF
Morente
Manolo M
MM
Piris
Miguel A
MA
García
Juan F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D016896:Treatment Outcome