title: Osteopontin expression in plasma of melanoma patients and in melanocytic tumours.
abstract: BACKGROUND
  While the serological tumour marker S100 is well established for the detection of metastatic melanoma, the extracellular matrix protein osteopontin (OPN) seems to be a promising novel marker for invasive melanoma.
  
  
  OBJECTIVE
  We analysed the potential of OPN as a serological tumour marker for metastatic melanoma and evaluated its combination with S100 and lactate dehydrogenase (LDH) levels to increase the reliability of these biomarkers for the detection of metastatic disease.
  
  
  METHODS
  We examined OPN in the peripheral blood of 110 melanoma patients using enzyme-linked immunosorbent assay and combined it with S100 and LDH levels. In addition, the protein expression of OPN was analysed in tissue sections of melanocytic nevi and melanomas of different progression stages by immunohistochemistry.
  
  
  RESULTS
  The independent comparison of S100 and OPN levels in metastatic vs. non-metastatic patients revealed a P-value <0.001 respectively. The predictiveness of OPN, S100 and LDH was 0.85, 0.89 and 0.69 as measured by the area under the receiver operating curve (AUC) respectively, while the combination of the two biomarkers OPN and S100 showed an AUC of 0.97. The optimal cut-off of the combination of OPN and S100 yielded a specificity of 85.9% and a sensitivity of 95.5%. By immunohistochemistry, OPN protein expression was detected in 29% (7/24) of melanocytic nevi, 67% (30/45) of primary melanomas and 39% (7/18) of metastatic melanomas.
  
  
  CONCLUSIONS
  Together, OPN seems to be a promising novel biomarker for the detection of metastatic disease in melanoma patients, showing elevated plasma levels in metastatic disease and increased protein expression in melanocytic lesions. The combination of OPN with the well-established tumour marker S100 might increase the prediction of metastases.
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University of Munich, Munich, Germany. tanja.maier@med.uni-muenchen.de
authors.forename: T
authors.initials: T
authors.lastname: Maier
authors.forename: R P
authors.initials: RP
authors.lastname: Laubender
authors.forename: R A
authors.initials: RA
authors.lastname: Sturm
authors.forename: A
authors.initials: A
authors.lastname: Klingenstein
authors.forename: H C
authors.initials: HC
authors.lastname: Korting
authors.forename: T
authors.initials: T
authors.lastname: Ruzicka
authors.forename: C
authors.initials: C
authors.lastname: Berking
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood*; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D009418:S100 Proteins / Q000097:blood; D012878:Skin Neoplasms / Q000097:blood*
chemical_list: D009418:S100 Proteins; D053495:Osteopontin; D007770:L-Lactate Dehydrogenase