title: Novel Humoral Prognostic Markers in Small-Cell Lung Carcinoma: A Prospective Study.
abstract: OBJECTIVE
  Favourable small cell lung carcinoma (SCLC) survival outcomes have been reported in patients with paraneoplastic neurological disorders (PNDs) associated with neuronal antibodies (Neur-Abs), but the presence of a PND might have expedited diagnosis. Our aim was to establish whether neuronal antibodies, independent of clinical neurological features, correlate with SCLC survival.
  
  
  METHODS
  262 consecutive SCLC patients were examined: of these, 24 with neurological disease were excluded from this study. The remaining 238 were tested for a broad array of Neur-Abs at the time of cancer diagnosis; survival time was established from follow-up clinical data.
  
  
  RESULTS
  Median survival of the non-PND cohort (n = 238) was 9.5 months. 103 patients (43%) had one or more antigen-defined Neur-Abs. We found significantly longer median survival in 23 patients (10%) with HuD/anti-neuronal nuclear antibody type 1 (ANNA-1, 13.0 months P = 0.037), but not with any of the other antigen-defined antibodies, including the PND-related SOX2 (n = 56, 24%). An additional 28 patients (12%) had uncharacterised anti-neuronal nuclear antibodies (ANNA-U); their median survival time was longer still (15.0 months, P = 0.0048), contrasting with the survival time in patients with non-neuronal anti-nuclear antibodies (detected using HEp-2 cells, n = 23 (10%), 9.25 months). In multivariate analyses, both ANNA-1 and ANNA-U independently reduced the mortality hazard by a ratio of 0.532 (P = 0.01) and 0.430 (P<0.001) respectively.
  
  
  CONCLUSIONS
  ANNAs, including the newly described ANNA-U, may be key components of the SCLC immunome and have a potential role in predicting SCLC survival; screening for them could add prognostic value that is similar in magnitude to that of limited staging at diagnosis.
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Gozzard
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chapman
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Bethan
authors.initials: B
authors.lastname: Lang
authors.affiliation: Division of Clinical Neuroscience, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Maddison
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology; D020361:Paraneoplastic Syndromes, Nervous System / Q000097:blood / Q000150:complications / Q000175:diagnosis; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000401:mortality*
chemical_list: D000912:Antibodies, Neoplasm; D009419:Nerve Tissue Proteins