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The utility of anti-SOX2 antibodies for cancer prediction in patients with paraneoplastic neurological disorders.

ABSTRACT: Antibodies to SOXB1 proteins in patients with paraneoplastic disorders are associated with small-cell lung cancer (SCLC), particularly in Lambert-Eaton myasthenic syndrome (LEMS). We aimed to establish if SOX2 antibodies could be used to identify SCLC and other tumours found in a range of paraneoplastic disorders and controls. SOX2 antibodies were detectable in 61% of patients with LEMS-SCLC, and in other paraneoplastic disorders, such as opsoclonus-myoclonus and paraneoplastic cerebellar degeneration, only when there was an underlying SCLC. SOX2 antibodies are specific (>90%) markers for SCLC, but are rarely found in patients with other tumours, whether neurological symptoms are present or not.

SUBMITTER: Maddison P

PROVIDER: S-EPMC6375907 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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The utility of anti-SOX2 antibodies for cancer prediction in patients with paraneoplastic neurological disorders.

Maddison Paul P Titulaer Maarten J MJ Verschuuren Jan J JJ Gozzard Paul P Lang Bethan B Irani Sarosh R SR Sabater Lidia L Graus Francesc F Murray Andrea A Chapman Caroline J CJ

Journal of neuroimmunology 20181108

Antibodies to SOXB1 proteins in patients with paraneoplastic disorders are associated with small-cell lung cancer (SCLC), particularly in Lambert-Eaton myasthenic syndrome (LEMS). We aimed to establish if SOX2 antibodies could be used to identify SCLC and other tumours found in a range of paraneoplastic disorders and controls. SOX2 antibodies were detectable in 61% of patients with LEMS-SCLC, and in other paraneoplastic disorders, such as opsoclonus-myoclonus and paraneoplastic cerebellar degene ...[more]

PMID: 30445363

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Project description:ImportanceLittle is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment.ObjectiveTo report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs.Design, setting, and participantsRetrospective case series study and immunological investigations conducted in February 2014 in a center for autoimmune neurological disorders. Fifteen cases with GAD65-abs evaluated between 1995 and 2013 who fulfilled criteria of definite or possible PNS without concomitant onconeural antibodies were included in this study.Main outcomes and measuresAnalysis of the clinical records of 15 patients and review of 19 previously reported cases. Indirect immunofluorescence with rat hippocampal neuronal cultures and cell-based assays with known neuronal cell-surface antigens were used. One hundred six patients with GAD65-abs and no cancer served as control individuals.ResultsEight of the 15 patients with cancer presented as classic paraneoplastic syndromes (5 limbic encephalitis, 1 paraneoplastic encephalomyelitis, 1 paraneoplastic cerebellar degeneration, and 1 opsoclonus-myoclonus syndrome). When compared with the 106 non-PNS cases, those with PNS were older (median age, 60 years vs 48 years; P = .03), more frequently male (60% vs 13%; P < .001), and had more often coexisting neuronal cell-surface antibodies, mainly against γ-aminobutyric acid receptors (53% vs 11%; P < .001). The tumors more frequently involved were lung (n = 6) and thymic neoplasms (n = 4). The risk for an underlying tumor was higher if the presentation was a classic PNS, if it was different from stiff-person syndrome or cerebellar ataxia (odds ratio, 10.5; 95% CI, 3.2-34.5), or if the patient had coexisting neuronal cell-surface antibodies (odds ratio, 6.8; 95% CI, 1.1-40.5). Compared with the current series, the 19 previously reported cases had more frequent stiff-person syndrome (74% vs 13%; P = .001) and better responses to treatment (79% vs 27%; P = .005). Predictors of improvement in the 34 patients (current and previously reported) included presentation with stiff-person syndrome and the presence of a thymic tumor.Conclusions and relevancePatients with GAD-abs must be screened for an underlying cancer if they have clinical presentations different from those typically associated with this autoimmunity or develop classic PNS. The risk for cancer increases with age, male sex, and the presence of coexisting neuronal cell-surface antibodies.

Dataset Information

The utility of anti-SOX2 antibodies for cancer prediction in patients with paraneoplastic neurological disorders.

Publications

The utility of anti-SOX2 antibodies for cancer prediction in patients with paraneoplastic neurological disorders.

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