Serum Soluble Syndecan-1 Levels at Diagnosis Constitute an Independent Prognostic Factor of Survival in Myeloma That May Further Differentiate Patients within the ISS Stages.

Syndecan-1 (CD138) is a heparin sulphate proteoglycan overexpressed on the surface of both normal and malignant plasma cells. Its role in multiple myeloma (MM) pathogenesis remains unclear. It may be shed from plasma cell surface and released in its soluble form (soluble syndecan-1: s-synd-1). Serum s-synd-1 levels have been shown to be a powerful prognostic factor of survival in myeloma patients. The role of s-synd-1 in the current prognostic classification systems requires further investigation. We have retrospectively determined soluble syndecan-1 in frozen sera of 99 MM patients, 18 MGUS patients, and 25 healthy individuals (HI). In all patients sera samples were collected at diagnosis. Serum s-synd-1 levels were determined by ELISA (Diaclone Research, Besanson, France) according to the manufacturer’s instructions. MM patients median age was 69 y (44–82), 51 were female, 48 male, 26 were Durie-Salmon (DS) stage I, 41 stage II, and 32 stage III while, according to the International Scoring System for MM (ISS), 32 were in stage 1, 25 in stage 2 and 42 in stage 3. Median serum s-synd-1 was 15 ng/ml (7–40) in HI, 16.5 ng/ml (8–220) in MGUS and 64 ng/ml (7–3500) in MM. Differences between HI and MM patients levels and between MGUS and MM patients levels were both significant (0.01 and 0.05 respectively). Overall survival was decreased in patients with elevated (mean + 2SD) serum s-synd-1 (5-year overall survival 35±9 vs 80±13, p=0.004). S-synd-1 levels were an independent prognostic factor of survival compared to DS and ISS staging systems. In multivariate analysis, only ISS and s-synd-1 were significant parameters of prognosis (the prognostic significance of DS, ISS and s-synd-1 was 0.06, 0.006 and 0.02 respectively). Further analysis of survival of patients stratified according to the ISS system showed a difference in survival within groups according to s-synd-1 levels. The 5-year overall survival was 100 vs 58±16 in ISS stage 1 patients with low or elevated s-synd-1 respectively, 100 vs 18±16 in stage 2 and 50±25 vs 14±13 in stage 3. The difference was statistically significant for stage 2 only (p=0.04) and there was only a trend due to the low number of patients in stages 1 and 3. In conclusion serum s-synd-1 levels at diagnosis constitute an independent prognostic factor of survival, able to further differentiate MM patients within the ISS stages.