title: Highly sensitive detection of melanoma at an early stage based on the increased serum secreted protein acidic and rich in cysteine and glypican-3 levels.
abstract: OBJECTIVE
  There are no available tumor markers detecting primary melanoma at an early stage. The identification of such serum markers would be of significant benefit for an early diagnosis of melanoma. We recently identified glypican-3 (GPC3) as a novel tumor marker but could diagnose only 40% of melanomas. Thereby, we focused out attention on secreted protein acidic and rich in cysteine (SPARC) overexpressed in melanoma as another candidate for tumor marker.
  
  
  METHODS
  Secreted SPARC protein was quantified using ELISA in the sera from 109 melanoma patients, five patients with large congenital melanocytic nevus, 61 age-matched healthy donors, and 13 disease-free patients after undergoing a surgical removal. We also quantified GPC3 and 5-S-cysteinyldopa in the same serum samples and compared these markers for their diagnostic value.
  
  
  RESULTS
  The serum SPARC concentrations in melanoma patients were greater than those in healthy donors (P = 0.001). When we fixed a cutoff value at the mean concentration plus 2 SD of the healthy donors, the serum SPARC was found to have increased in the sera of 36 of the 109 (33%) melanoma patients, whereas there were three (4.9%) false-positive cases of 61 healthy donors. Surprisingly, 19 of 36 patients showing increased SPARC levels were in stages 0 to II. The serum SPARC level decreased under the cutoff level in 10 of 13 patients after surgical removal. Using SPARC and GPC3 in combination thus enabled us to diagnose 47 of 75 (66.2%) melanoma patients at an early stage (0-II).
  
  
  CONCLUSIONS
  SPARC or its combination with GPC3 is thus considered a potentially useful tumor marker, especially for melanoma at an early stage.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ikuta
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kageshita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukushima
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D017077:Culture Media, Conditioned / Q000737:chemistry; D003548:Cysteinyldopa; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000097:blood*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D015676:Osteonectin / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D015676:Osteonectin; D012333:RNA, Messenger; D003548:Cysteinyldopa