Longitudinal analysis and prognostic effect of cancer-testis antigen expression in multiple myeloma.
OBJECTIVE
Reliable data on the persistence of tumor expression of cancer-testis (CT) antigens over time and consequent analyses of the effect of CT antigen expression on the clinical course of malignancies are crucial for their evaluation as diagnostic markers and immunotherapeutic targets.


METHODS
Applying conventional reverse transcription-PCR, real-time PCR, and Western blot, we did the first longitudinal study of CT antigen expression in multiple myeloma analyzing 330 bone marrow samples from 129 patients for the expression of four CT antigens (MAGE-C1/CT7, MAGE-C2/CT10, MAGE-A3, and SSX-2).


RESULTS
CT antigens were frequently and surprisingly persistently expressed, indicating that down-regulation of these immunogenic targets does not represent a common tumor escape mechanism in myeloma. We observed strong correlations of CT antigen expression levels with the clinical course of myeloma patients as indicated by the number of bone marrow-residing plasma cells and peripheral paraprotein levels, suggesting a role for CT antigens as independent tumor markers. Investigating the prognostic value of CT antigen expression in myeloma patients after allogeneic stem cell transplantation, we found that expression of genes, such as MAGE-C1, represents an important indicator of early relapse and dramatically reduced survival.


CONCLUSIONS
Our findings suggest that CT antigens might promote the progression of multiple myeloma and especially MAGE-C1/CT7, which seems to play the role of a "gatekeeper" gene for other CT antigens, might characterize a more malignant phenotype. Importantly, our study also strongly supports the usefulness of CT antigens as diagnostic and prognostic markers as well as therapeutic targets in myeloma.
Atanackovic
Djordje
D
Department of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. D.Atanackovic@uke.uni-hamburg.de
Luetkens
Tim
T
Hildebrandt
York
Y
Arfsten
Julia
J
Bartels
Katrin
K
Horn
Christiane
C
Stahl
Tanja
T
Cao
Yanran
Y
Zander
Axel R
AR
Bokemeyer
Carsten
C
Kröger
Nicolaus
N
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D011379:Prognosis; D012097:Repressor Proteins / Q000032:analysis*
D000951:Antigens, Neoplasm; C072013:MAGEA3 protein, human; C110905:MAGEC1 protein, human; C405429:MAGEC2 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins