SOX2 antibody responses in patients with various tumor types and SCLC with and without paraneoplastic neurologic syndromes

Abstract

2562 Background: SOX2, a member of the SOX Group B family of transcription factors, is expressed in normal adult brain, testis and prostate as well as in many SCLC cell lines. Spontaneous antibody responses to SOX2 have previously been shown to be detectable in SCLC patients. We undertook a retrospective study to determine whether antibody responses were detectable in patients with other malignancies and in patients with paraneoplastic neurologic syndromes (PND/PNS). Methods: Previously obtained serum samples from patients with no known disease (n = 84), breast and ovarian cancer (n = 35 each), melanoma (n = 42), NSCLC (n = 150), and SCLC patients, 90 from Turkey and 68 patients studied for PND, were tested by ELISA using serial 4-fold dilutions for anti-SOX2 and anti-HuD antibody. Results: Preliminary data shows SOX2 reactivity in 5/84 (6%) normal volunteer sera, 8/35 (23%) in both breast and ovarian cancer patients, 4/42 (9%) melanoma patients, 20/150 (13.3%) NSCLC patients, and 56/158 (35.4%) SCLC patients. Compared to controls, there was a statistically significant difference in SOX2 immunoreactivity in breast, ovarian (p = 0.007 for both) and SCLC patients (p < 0.001), and a trend was noted in NSCLC patients (p = 0.080). No breast, ovarian, melanoma or normal patient had SOX2 antibody titers ≥1:6400, compared with 32/56 (57.1%) of SCLC (p < 0.01) and 6/20 (30%) NSCLC patients (p < 0.16). Nine SCLC patients had neurologic symptoms and were previously found to have anti-HuD antibodies, associated with a diagnosis of PND. This was confirmed in 8/9 patients in our assay. However, none of the nine patients displayed anti-SOX2 reactivity. Eleven additional SCLC patients were found to be HuD positive by our ELISA. Conclusions: Anti-SOX2 responses are found in a significant proportion of patients with SCLC, breast and ovarian cancer, but not in melanoma patients compared to normal controls. Patients with SCLC have higher titer antibodies when compared with the other groups, and anti-SOX2 antibodies do not appear to associate with anti-HuD responses, supporting the hypothesis that SOX2 immune responses are not associated with PND and may be useful as a vaccine target. Supported by the Cancer and Leukemia Group B/Aventis Oncology Award and the Steps for Breath Foundation. No significant financial relationships to disclose.