Serum syndecan-1, basic fibroblast growth factor and osteoprotegerin in myeloma patients at diagnosis and during the course of the disease.
Neovascularisation and bone resorption are related to myeloma disease activity.


OBJECTIVE
To investigate the possible prognostic importance of serum syndecan-1, basic fibroblast growth factor (bFGF) and osteoprotegerin (OPG) levels, the relationship between them, with parameters of disease activity and the effect of treatment on their levels.


METHODS
Twenty-seven patients were studied from diagnosis and an additional five from remission, for a median follow-up of 40 months. Twenty-three patients received chemotherapy plus bisphosphonates and nine only bisphosphonates. Sera from 11 healthy individuals (HI) were used as controls. Cytokines were determined by commercially available enzyme-linked immunosorbent assays (ELISA) kits.


RESULTS
In HI, median syndecan-1 was 40 ng/mL (28-75), bFGF 8 pg/mL (7-30), OPG 35 pg/mL (4-100). Pretreatment median serum syndecan-1 was 177.5 ng/mL (34-3500), bFGF 11.5 pg/mL (8-65) and OPG 100 pg/mL (4-1000). Pretreatment syndecan-1, bFGF and OPG serum levels were increased in patients compared with HI (P = 0.001, 0.03 and 0.01, respectively). Syndecan-1 and bFGF levels were correlated with stage (P = 0.004 and 0.03, respectively). Both syndecan-1 and OPG levels were correlated with beta2M (P = 0.04 and 0.01, respectively). Patients with elevated syndecan-1 and bFGF serum levels had shorter survival than patients with normal levels (P = 0.01 and 0.05, respectively). After chemotherapy syndecan-1 and OPG levels were found to be decreased in responders and syndecan-1 level was reduced in patients receiving bisphosphonates alone.


CONCLUSIONS
Pretreatment syndecan-1, bFGF and OPG levels were found to be increased at diagnosis. Syndecan-1 and OPG fluctuated according to MM activity. Elevated serum syndecan-1 and bFGF levels predicted short survival.
Kyrtsonis
Maria-Christina
MC
Hematology Section and Research Laboratory, First Department of Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, Laikon General Hospital, Athens, Greece.
Vassilakopoulos
Theodoros P
TP
Siakantaris
Marina P
MP
Kokoris
Styliani I
SI
Gribabis
Despina A
DA
Dimopoulou
Maria N
MN
Angelopoulou
Maria K
MK
Pangalis
Gerassimos A
GA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001862:Bone Resorption / Q000097:blood / Q000209:etiology; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004164:Diphosphonates / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D015993:Life Tables; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D009363:Neoplasm Proteins / Q000097:blood*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000097:blood / Q000209:etiology; D053244:Osteoprotegerin; D000077268:Pamidronate; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011509:Proteoglycans / Q000097:blood*; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D016019:Survival Analysis; D053668:Syndecan-1; D053667:Syndecans; D014750:Vincristine / Q000008:administration & dosage; D001613:beta 2-Microglobulin / Q000032:analysis
D014408:Biomarkers, Tumor; D004164:Diphosphonates; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D053244:Osteoprotegerin; D011509:Proteoglycans; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; C506030:TNFRSF11B protein, human; D001613:beta 2-Microglobulin; D016222:Fibroblast Growth Factor 2; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077268:Pamidronate; D008558:Melphalan; D011241:Prednisone