Recent studies have identified antibodies to the SOXB1 group of proteins in patients with paraneoplastic disorders (PNDs) associated with small-cell lung cancer (SCLC), particularly Lambert-Eaton myasthenic syndrome (LEMS), but rarely in non-tumour LEMS, indicating that these antibodies may be useful paraneoplastic biomarkers. We aimed to establish if SOX antibodies could be used to identify underlying tumours in a range of PNDs, including control tumour groups. We established a SOX2 ELISA with high test-retest reproducibility. Positivity to SOX2 in control patients without neurological symptoms was 77/259 (30%) in SCLC, but only 15/238 (6%) in non-SCLC, 0/75 in breast cancer, 3/104 (3%) in ovarian cancer, and 12/414 (3%) in age matched healthy controls. Antibodies to SOX2 were detected in 39/71 (55%) patients with LEMS-SCLC, and 7/105 (6.6%) patients with non-tumour LEMS (p<0.0001). SOX2 antibodies were detected in 9/19 (47%) patients with paraneoplastic cerebellar degeneration, exclusively with co-existent LEMS (9/16), but not in idiopathic late onset cerebellar ataxia (0/23). We found SOX2 antibodies in 3/9 (33%) opsoclonus-myoclonus-SCLC patients, but in only 1/10 (10%) adult idiopathic OMS, but not at all in teratoma-related (0/8), or non-tumour associated (0/10) NMDAr antibody encephalitis, nor myasthenia with thymoma (0/28). Thus SOX2 antibodies are specific (>90%) markers for SCLC, but not other tumours, in patients with PNDs, particularly LEMS with or without ataxia.
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