Originally published as JCO Early Release 10.1200/JCO.2008.20.6169 on August 10 2009

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SOX Antibodies in Small-Cell Lung Cancer and Lambert-Eaton Myasthenic Syndrome: Frequency and Relation With Survival

Maarten J. Titulaer, Rinse Klooster, Marko Potman, Lidia Sabater, Francesc Graus, Ingrid M. Hegeman, Peter E. Thijssen, Paul W. Wirtz, Albert Twijnstra, Peter A.E. Sillevis Smitt, Silvère M. van der Maarel, Jan J.G.M. Verschuuren

From the Departments of Neurology and Human Genetics, Leiden University Medical Center, Leiden; Department of Neurology, Haga Hospital, the Hague; Department of Neurology, University Hospital Maastricht, Maastricht; Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology, Hospital Clinic, Universitat de Barcelona; and Institut d' Investigació Biomèdica August Pi i Sunyer, Barcelona, Spain.

Corresponding author: Maarten J. Titulaer, MD, Department of Neurology, J3-R-166, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands; e-mail: m.j.titulaer{at}lumc.nl.

Purpose SOX1 antibodies are common in small-cell lung carcinoma (SCLC) with and without paraneoplastic syndrome (PNS) and can serve as serological tumor marker. Addition of other antibodies might improve its diagnostic power. We validated an enzyme-linked immunosorbent assay (ELISA) to assess the diagnostic value of serum antibodies in SCLC and Lambert-Eaton myasthenic syndrome (LEMS). Clinical outcome with respect to SOX antibodies was evaluated, as the SOX-related antitumor immune response might help to control the tumor growth.

Patients and Methods We used recombinant SOX1, SOX2, SOX3, SOX21, HuC, HuD, or HelN1 proteins in an ELISA to titrate serum samples and validated the assay by western blot. We tested 136 consecutive SCLC patients, 86 LEMS patients (43 with SCLC), 14 patients with SCLC and PNS (paraneoplastic cerebellar degeneration or Hu syndrome), 62 polyneuropathy patients, and 18 healthy controls.

Results Our ELISA was equally reliable as western blot. Forty-three percent of SCLC patients and 67% of SCLC-LEMS patients had antibodies to one of the SOX or Hu proteins. SOX antibodies had a sensitivity of 67% and a specificity of 95% to discriminate between LEMS with SCLC and nontumor LEMS. No difference in survival was observed between SOX positive and SOX negative SCLC patients.

Conclusion SOX antibodies are specific serological markers for SCLC. Our assay is suitable for high throughput screening, detecting 43% of SCLC. SOX antibodies have diagnostic value in discriminating SCLC-LEMS from nontumor LEMS, but have no relation to survival in patients with SCLC.

*M.J.T. and R.K. contributed equally to this article.

Supported in part by the Leiden University Medical Center, the European Union research project "PNSEuronetwork" contract number LSSM-CT 2005-518174, and the Prinses Beatrix Fonds.

Presented in part at the 9th International Congress of NeuroImmunology, October 26-30, 2008, Fort Worth, TX.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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