Frequency of SOX Group B (SOX1, 2, 3) and ZIC2 antibodies in Turkish patients with small cell lung carcinoma and their correlation with clinical parameters

BACKGROUND Expression of neuroectodermal markers is a key feature of small cell lung carcinoma (SCLC). Although immune responses against a number of these proteins have been associated with paraneoplastic neuronal disease (PND), most patients with SCLC have anti‐neuroectodermal antibodies in the absence of PND. Whether these immune responses affect the clinical outcome in SCLC is critical in understanding the potential value of these proteins as cancer vaccine targets as well as in the pathogenesis of PND. METHODS The authors investigated the frequency of immunoglobulin G autoantibodies against Sry‐like high‐mobility group box (SOX)1, 2, 3 and Zinc‐finger gene of the cerebellum (ZIC)2 proteins in stored serum samples from 90 patients utilizing the λ‐phage plaque assay. Data obtained from patient records were utilized to measure clinical correlates of seroreactivity. RESULTS Antibodies to SOX1 were present in 28% of patients and another 28% had anti‐ZIC2 antibodies, classifying these as some of the most frequent antibody responses observed in SCLC. None had autoimmune paraneoplastic disease. Antibody titers were frequently as high as ≥ 1:106 and were stable for ≤ 6 months after diagnosis. Seroreactivity against either SOX1 or ZIC2 correlated with younger age, lower lactate dehydrogenase levels, and better response to initial therapy. CONCLUSIONS The frequent and stable presence of SOX Group B and/or ZIC2 antibodies in SCLC, but not in healthy individuals examined, indicates they are serological markers of SCLC. However, the correlation between known clinical parameters of less aggressive disease and seroreactivity suggests that these antibodies are indicators of better prognosis in SCLC and warrants further studies to clarify the nature of the underlying immune responses. Cancer 2005. © 2005 American Cancer Society. The authors described anti–Sry‐like high mobility group box (SOX) Group B and Zinc‐finger gene of the cerebellum (ZIC)2 antibodies as two of the most frequently observed antigenic reactivities in small cell lung carcinoma. The association of these antibodies with parameters of more indolent disease, in the absence of paraneoplastic disease, suggested that SOX Group B and ZIC2 antigens can potentially be good therapeutic targets for immunotherapy. The authors reported that further studies are warranted to understand the underlying immune response.