Originally published as JCO Early Release 10.1200/JCO.2008.18.0554 on March 23 2009

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Serum Amyloid A As a Prognostic Marker in Melanoma Identified by Proteomic Profiling

Peter Findeisen, Marc Zapatka, Teresa Peccerella, Heike Matzk, Michael Neumaier, Dirk Schadendorf, Selma Ugurel

From the Institute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg; Department of Theoretical Bioinformatics, German Cancer Research Center; Skin Cancer Unit, German Cancer Research Center Heidelberg, Heidelberg; and the Department of Dermatology, University Hospital of Mannheim, Mannheim, Germany.

Corresponding author: Selma Ugurel, MD, Department of Dermatology, Julius-Maximilians-University, Josef-Schneider-Strasse 2, 97080 Wuerzburg, Germany; e-mail: ugurel_s{at}klinik.uni-wuerzburg.de.

Purpose Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers.

Patients and Methods Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays.

Results MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival.

Conclusion SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.

*P.F. and M.Z. contributed equally to this work.

Supported by a grant from the German Cancer Aid/Deutsche Krebshilfe (proposal No. 106856) and by the German Federal Ministry of Research and Education through research grant No. 01 GR 0450 in the National Genome Research Network.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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