title: Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status.
abstract: BACKGROUND
  Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear.
  
  
  OBJECTIVE
  To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers.
  
  
  METHODS
  In total, 162 patients with stage IV melanoma and known BRAF mutation status were included. Clinical, histopathological and laboratory information was collected and compared between patients with BRAF mutant (BRAFm) and wild-type (BRAFwt) melanoma at the time of first distant metastasis.
  
  
  RESULTS
  In total, 88 patients (54%) had BRAFm melanoma (V600E/V600K). At the first distant metastasis, S100B levels in BRAFm patients were more frequently elevated (P = 0·01) and significantly higher (P = 0·02). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared with patients with elevated S100B levels (P < 0·01). In BRAFm melanoma, elevated S100B levels showed no prognostic influence (P = 0·18). Elevated lactate dehydrogenase (LDH) levels had a significantly negative impact on mOS in both groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared with BRAFm patients not receiving BRAFi (P = 0·01). No difference in mOS between BRAFm patients who did not receive BRAFi treatment and BRAFwt patients was observed.
  
  
  CONCLUSIONS
  Better mOS was observed in BRAFm patients treated with BRAFi. BRAFm patients not treated with BRAFi show similar survival curves to BRAFwt patients. Elevated LDH is a BRAF-independent prognostic parameter; S100B has prognostic significance in BRAFwt melanoma only.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091, Zurich, Switzerland.
authors.forename: A L
authors.initials: AL
authors.lastname: Frauchiger
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Mangana
authors.affiliation: Department of Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Rechsteiner
authors.affiliation: Department of Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Moch
authors.affiliation: Epidemiology, Biostatistics and Prevention Institute, Department of Biostatistics, University of Zurich, Zurich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Seifert
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091, Zurich, Switzerland.
authors.forename: R P
authors.initials: RP
authors.lastname: Braun
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091, Zurich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Dummer
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091, Zurich, Switzerland.
authors.forename: S M
authors.initials: SM
authors.lastname: Goldinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D007770:L-Lactate Dehydrogenase; D048493:Proto-Oncogene Proteins B-raf