SOX antibodies in small-cell lung cancer and Lambert-Eaton myasthenic syndrome: frequency and relation with survival.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Titulaer
Maarten J
MJ
Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands. m.j.titulaer@lumc.nl
Klooster
Rinse
R
Potman
Marko
M
Sabater
Lidia
L
Graus
Francesc
F
Hegeman
Ingrid M
IM
Thijssen
Peter E
PE
Wirtz
Paul W
PW
Twijnstra
Albert
A
Smitt
Peter A E Sillevis
PA
van der Maarel
Silvère M
SM
Verschuuren
Jan J G M
JJ
D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood; D015153:Blotting, Western; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000175:diagnosis / Q000276:immunology*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000175:diagnosis / Q000276:immunology; D055748:SOXB1 Transcription Factors / Q000276:immunology*; D012680:Sensitivity and Specificity; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis / Q000276:immunology*; D016019:Survival Analysis
D001323:Autoantibodies; D014408:Biomarkers, Tumor; D055748:SOXB1 Transcription Factors