Sukru Atakan1, Hulya Bayiz2, Serpil Sak3, Alper Poyraz1, Burcak Vural4, Azmi Serhat Yildirim1, Funda Demirag5, Ali Osmay Gure1. 1. Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey. 2. Department of Thoracic Medicine, Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey. 3. Department of Pathology, Ankara University, Ankara, Turkey. 4. Department of Genetics, Institute for Experimental Medicine, Istanbul University School of Medicine, Istanbul, Turkey. 5. Department of Pathology, Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey.
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. CONCLUSION: 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.
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 SCLCpatients 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. CONCLUSION: 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.
Entities:
Keywords:
Autologous antibodies; Autologous antibody responses; Cancer stem cells; Cancer stem-cells; Immunohistochemistry; Lung cancer; Tumor antigens; Tumor immunology
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