title: Autologous anti-SOX2 antibody responses reflect intensity but not frequency of antigen expression in small cell lung cancer.
abstract: BACKGROUND
  Anti-SOX2 antibody responses are observed in about 10 to 20% of small cell lung cancer (SCLC) patients. The aim of this study was to determine whether such responses reflect a particular pattern of SOX2 protein expression in the tumor and whether this pattern associates with clinical outcome.
  
  
  METHODS
  Paraffin embedded tumor tissues, obtained from SCLC patients who had no evidence of paraneoplastic autoimmune degeneration, were evaluated for SOX2 expression by immunohistochemistry for both intensity and extent of staining. Sera from the same patients were tested for autologous antibodies against recombinant SOX2 by enzyme-linked immunosorbent assay (ELISA). Correlates between overall survival and various clinical parameters including SOX2 staining and serology were determined.
  
  
  RESULTS
  SOX2 protein expression was observed in tumor tissue in 89% of patients. Seventeen patients (29%) were seropositive for SOX2 antibodies and, in contrast to SOX2 staining, the presence of antibody correlated with limited disease stage (p = 0.05). SOX2 seropositivity showed a significant association with the intensity of SOX2 staining in the tumor (p = 0.02) but not with the frequency of SOX2 expressing cells.
  
  
  CONCLUSIONS
  Anti-SOX2 antibodies associate with better prognosis (limited stage disease) while SOX2 protein expression does not; similar to reports from some earlier studies. Our data provides an explanation for this seemingly contrasting data for the first time as SOX2 antibodies can be observed in patients whose tumors contain relatively few but strongly staining cells, thus supporting the possible presence of active immune-surveillance and immune-editing targeting SOX2 protein in this tumor type.
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey.
authors.forename: Sukru
authors.initials: S
authors.lastname: Atakan
authors.affiliation: Department of Thoracic Medicine, Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey.
authors.forename: Hulya
authors.initials: H
authors.lastname: Bayiz
authors.affiliation: Department of Pathology, Ankara University, Ankara, Turkey.
authors.forename: Serpil
authors.initials: S
authors.lastname: Sak
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey.
authors.forename: Alper
authors.initials: A
authors.lastname: Poyraz
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University School of Medicine, Istanbul, Turkey.
authors.forename: Burcak
authors.initials: B
authors.lastname: Vural
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey.
authors.forename: Azmi Serhat
authors.initials: AS
authors.lastname: Yildirim
authors.affiliation: Department of Pathology, Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey.
authors.forename: Funda
authors.initials: F
authors.lastname: Demirag
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey.
authors.forename: Ali Osmay
authors.initials: AO
authors.lastname: Gure
keywords: Autologous antibodies; Autologous antibody responses; Cancer stem cells; Cancer stem-cells; Immunohistochemistry; Lung cancer; Tumor antigens; Tumor immunology