title: The dynamics of serum tumor markers in predicting metastatic uveal melanoma (part 1).
abstract: OBJECTIVE
  To examine the kinetics of the tumor marker levels: osteopontin (OPN), S-100β, melanoma inhibitory activity (MIA) and tissue polypeptide-specific antigen (TPS), and to evaluate their potential for predicting earlier liver metastasis in patients with uveal melanoma (UM).
  
  
  METHODS
  Forty-three UM patients who remained disease-free (DF) for at least 10 years, 32 patients with metastatic UM and 53 healthy controls were enrolled. Median and mean levels of the tumor markers OPN, S-100β, MIA and TPS at the time periods of 0-6, 6-12, 12-18, 18-24 and >24 months prior to confirmation of metastasis by liver ultrasound, CT scan and biopsy, served in a box and whiskers analysis and were compared by Students t-test. Trends of changes in marker levels of DF and metastatic UM groups were calculated and compared by ANOVA.
  
  
  RESULTS
  The lead-time for predicting metastasis was: 12-18 months both for OPN (p=0.005) and MIA (p=0.37), for S-100β 18-24 months first increase (p=0.5) followed by a second one 0-6 months (p=0.01) and for TPS 18-24 months (p=0.1). The gradient of the trendlines for the metastatic group was significantly steeper for MIA (p=0.02) and S-100β (p=0.018) than for the DF group and not statistically significant for OPN (p=0.168). For TPS, the trendline was negative. The overall increase in the levels of OPN and S-100β was significant, while for TPS and MIA, it was not.
  
  
  CONCLUSIONS
  Significant increases in OPN and S-100β levels were demonstrated by a major lead time. Trendlines of the metastasis group were steeper than of the DF group predicting liver metastasis. The routine use of those markers in the follow up of UM patients, can enable earlier diagnosis of liver metastasis and effective therapeutic intervention, with an impact on survival.
authors.affiliation: Immunology Laboratory for Tumor Diagnosis, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. barakvivi@hadassah.org.il
authors.forename: Vivian
authors.initials: V
authors.lastname: Barak
authors.forename: Igor
authors.initials: I
authors.lastname: Kaiserman
authors.forename: Shahar
authors.initials: S
authors.lastname: Frenkel
authors.forename: Keren
authors.initials: K
authors.lastname: Hendler
authors.forename: Inna
authors.initials: I
authors.lastname: Kalickman
authors.forename: Jacob
authors.initials: J
authors.lastname: Pe'er
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000556:secondary; D008545:Melanoma / Q000097:blood / Q000473:pathology; D009363:Neoplasm Proteins / Q000097:blood; D009414:Nerve Growth Factors / Q000097:blood; D053495:Osteopontin / Q000097:blood; D010455:Peptides / Q000097:blood; D011379:Prognosis; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000097:blood / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D010455:Peptides; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C089984:tissue polypeptide specific antigen; D053495:Osteopontin