SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs

• Published in: Journal of immunotherapy (1997) Vol. 28; no. 6; p. 564
• Main Authors: Taylor, Brian J, Reiman, Tony, Pittman, Julie A, Keats, Jonathan J, de Bruijn, Diederik R H, Mant, Michael J, Belch, Andrew R, Pilarski, Linda M
• Format: Journal Article
• Language: English
• Published: United States 01.11.2005
• Subjects: Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - genetics; Cancer Vaccines; Cell Line; Gene Expression Regulation, Neoplastic; Humans; Male; Multiple Myeloma - genetics; Multiple Myeloma - immunology; Multiple Myeloma - metabolism; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Paraproteinemias - genetics; Paraproteinemias - immunology; Paraproteinemias - metabolism; Plasma Cells - immunology; Plasma Cells - metabolism; Prognosis; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - biosynthesis; Survival Analysis; Testis - immunology
• ISSN: 1524-9557
• DOI: 10.1097/01.cji.0000175685.36239.e5

Cancer testis antigens (CTAs) are tumor-specific antigens that may be useful targets for cancer vaccines. Here, CTA expression was examined in multiple myeloma (MM), a B-cell cancer characterized by malignant plasma cells (PCs) in the bone marrow (BM), and monoclonal gammopathy of undetermined significance (MGUS), a condition that can progress to MM. We screened a panel of patient BMs at different stages of malignancy for CTA expression by reverse transcription polymerase chain reaction RT-PCR. Here, SSX (synovial sarcoma, X chromosome) emerged as a promising candidate for an MM vaccine, having a profile similar to currently studied CTA, NY-ESO-1, and MAGE. SSX1, 2, 4, and 5 expression was studied further in 114 MM (total SSX, 61% of patients; SSX1, 42%; SSX2, 23%; SSX4, 38%; SSX5, 35%), 45 MGUS (total SSX, 24% of patients; SSX1, 9%; SSX4, 20%), and 12 control (0/12, 0%) subjects. Several expression patterns were observed, the most predominant being co-expression of SSX1, 2, 4, and 5 (called group A expression, in 20% of MM), which correlated with reduced survival (P=0.0006). Of the four genes, SSX2 had the strongest association with reduced survival (P=0.0001). SSX protein expression ranged from 13.5% of PCs in an SSX1/SSX4 co-expressor to as high as 88% of PCs in group A expressor, exceeding reported frequencies of NY-ESO-1 and MAGE in MM. In single PCs from group A patients, we detected variable degrees of SSX co-expression, emphasizing the heterogeneity of CTA expression within tumor cell populations. These results demonstrate that SSX is a frequently expressed CTA in MM and highlight its potential as an MM vaccine candidate.