title: Diagnostic accuracy and predictive value of the tumor-associated antigen S100 in malignant melanomas: validation by whole body FDG-PET and conventional diagnostics.
abstract: We investigated the predictive value of the protein S100 as a tumor-marker in the post-surgical follow-up staging of patients with High Risk melanomas (Clark Levels IV/V, Thickness > 0.75 mm).
  
  
  METHODS
  In 51 follow-up studies, performed in 50 patients, serum concentrations of the protein S100 were measured and evaluated with respect to their diagnostic value based on the findings of whole body F-18-FDG-PET studies. The findings of FDG-PET were correlated with the findings of CT, MRI, lymph node sonography, bone scintigraphy, and with histological findings, or a follow-up staging after at least 6 months, respectively. Thus, FDG-PET exhibited a sensitivity of 100% and a specificity of 95%. S100 concentrations were measured by an established RIA (Ria-mat Sangtec 100) and by a novel LIA (Lia-mat Sangtec 100 beta). Subsequently, S100 was compared with thymidine kinase for the predictive values of both tumor-markers in the follow-up of malignant melanoma.
  
  
  RESULTS
  Intraindividual comparison of S100 concentrations measured by LIA with those obtained by RIA showed a calculated correlation coefficient of 0.97 (Cutoff-levels were 0.1 microgram/l [RIA] and 0.2 microgram/l [LIA]). The arrangement of these cutoff-levels leads to a sensitivity of 85% at a specificity of 55% for Protein S100 when measured by RIA, and to a sensitivity of 77% at a specificity of 61% when measured by LIA. The negative predictive values are 91% (RIA) and 88% (LIA), in association with positive predictive values of 39% (RIA) and 40% (LIA). At a cutoff-level of 4.0 micrograms/l, thymidine kinase showed a sensitivity of 70% and a specificity of 41%.
  
  
  CONCLUSIONS
  a) The results obtained by LIA are in a very good correlation with the results measured by the well-established RIA. Thus, the LIA is a suitable method for the clinical routine. b) The protein S100 as a tumor-marker of malignant High Risk melanomas has no clinically important sensitivity and specificity as could be proved by a comparison with the predictive value of FDG-PET. c) Whether or not during therapy information concerning progression/remission of the disease can be received out of repetitive measurements of the S100, has to be shown by the results of validated long term follow-up studies.
authors.affiliation: Klinik für Nuklearmedizin, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Mruck
authors.forename: R P
authors.initials: RP
authors.lastname: Baum
authors.forename: D
authors.initials: D
authors.lastname: Rinne
authors.forename: G
authors.initials: G
authors.lastname: Hör
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007118:Immunoassay; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011863:Radioimmunoassay; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012189:Retrospective Studies; D009418:S100 Proteins / Q000097:blood*; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D013937:Thymidine Kinase / Q000097:blood; D014055:Tomography, Emission-Computed
chemical_list: D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D009418:S100 Proteins; C110294:S100A1 protein; D019788:Fluorodeoxyglucose F18; D013937:Thymidine Kinase