Expression and prognostic relevance of MAGE-C1/CT7 and MAGE-C2/CT10 in osteolytic lesions of patients with multiple myeloma.
Cancer-testis (CT) antigens are promising targets for antigen-specific therapy of multiple myeloma (MM). Osteolytic lesions represent the most common clinical manifestation of myeloma and it is possible that osseous myeloma lesions differ from bone-infiltrating tumor cells with regard to the extent of CT antigen expression based on the epigenetic regulation of these genes. We, therefore, performed the first analysis of CT antigen expression in osteolytic lesions of myeloma patients to further define the diagnostic, prognostic, and therapeutic value of these proteins. Lytic bone samples were obtained from MM patients during surgical interventions and a tissue microarray was constructed. 105 bone samples and 24 bone marrow biopsies were stained immunohistochemically with antibodies against CT antigens MAGE-C1/CT7 and MAGE-C2/CT10 and Ki-67. MAGE-C1/CT7 and MAGE-C2/CT10 were frequently expressed in osteolytic lesions (46% and 54%) and bone marrow (75% and 54%). Expression of MAGE-C1/CT7 was significantly more frequent in patients with advanced stage of disease (p=0.023) and with a chromosomal deletion 17p13 (p53) (p=0.047). Samples with more than 75% MAGE-C1/CT7 expressing myeloma cells showed a higher proliferative rate (indicated by the expression of Ki67) than those with less than 25% MAGE-C1/CT7 expressing cells (p=0.011). Moreover, a content of ≥50% MAGE-C1/CT7 expressing myeloma cells in a sample was associated with reduced overall survival (p=0.013). Our results, therefore, suggest that expression of MAGE-C1/CT7 and MAGE-C2/CT10 in osteolytic lesions of myeloma patients can be used for diagnostic, prognostic, as well as immunotherapeutic purposes.
Pabst
Caroline
C
Department of Oncology/Hematology/Bone Marrow Transplantation with the section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Zustin
Jozef
J
Jacobsen
Frank
F
Luetkens
Tim
T
Kröger
Nicolaus
N
Schilling
Georgia
G
Bokemeyer
Carsten
C
Sauter
Guido
G
Atanackovic
Djordje
D
Marx
Andreas
A
D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010014:Osteolysis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
D000951:Antigens, Neoplasm; C110905:MAGEC1 protein, human; C405429:MAGEC2 protein, human; D009363:Neoplasm Proteins