title: B-Raf specific antibody responses in melanoma patients.
abstract: BACKGROUND
  Mutations of the BRAF gene are the most common genetic alteration in melanoma. Moreover, BRAF mutations are already present in benign nevi. Being overexpressed and mutated, B-Raf is a potential target for the immune system and as this mutation seems to be an early event, a humoral immune response against this antigen might serve as a diagnostic tool for detection of high risk patients.
  
  
  METHODS
  372 sera of 148 stage IV melanoma patients and 119 sera of non-melanoma patients were screened for B-Raf, B-Raf V599E and C-Raf specific antibodies by an ELISA assay. Sera were screened for specific total Ig and for IgG. Serum titers were compared with a two tailed Mann-Whitney U test. Sera with titers of 1:300 or higher were termed positive and groups were compared with a two tailed Fisher's exact test.
  
  
  RESULTS
  B-Raf specific antibodies recognizing both B-Raf and B-Raf V599E were detected in 8.9% of the sera of melanoma patients and in 2,5% of the control group. Raf specific IgG was detected in some patients at very low levels. B-Raf specific antibody responses did not correlate with clinical parameters but in some cases, B-Raf antibodies emerged during disease progression.
  
  
  CONCLUSIONS
  These findings imply that B-Raf is immunogenic in melanoma patients and that it might serve as a potential target for immunotherapy. However, B-Raf specific antibodies emerge at rather late stages of melanoma progression and are present only with a low frequency indicating that spontaneous B-Raf specific antibodies are not an early marker for melanoma, but rather may serve as a therapeutic target.
authors.affiliation: Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University Clinics of Würzburg, Versbacher Str. 5, 97078 Würzburg, Germany. joachim.fensterle@mail.uni-wuerzburg.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Fensterle
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Tamara
authors.initials: T
authors.lastname: Potapenko
authors.forename: Veronika
authors.initials: V
authors.lastname: Heimbach
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Vetter
authors.forename: Eva B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Rapp
mesh_terms: D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D000918:Antibody Specificity; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008545:Melanoma / Q000276:immunology*; D048493:Proto-Oncogene Proteins B-raf / Q000276:immunology*; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf