title: Cancer and systemic sclerosis:  novel insights into pathogenesis and clinical implications.
abstract: OBJECTIVE
  Most epidemiologic studies have demonstrated an increased risk of cancer in scleroderma patients. Reasons for this risk increase have been poorly understood and often attributed to cytotoxic therapies or damage from scleroderma. Recognition that some patients have a close temporal relationship between cancer diagnosis and scleroderma clinical onset has focused attention on the possibility that scleroderma may be a paraneoplastic syndrome in a subset of patients. This review will discuss the latest epidemiologic data linking cancer and scleroderma and explore a model for the development of paraneoplastic scleroderma.
  
  
  RESULTS
  New investigations have demonstrated an association between RNA polymerase III autoantibodies and a close temporal relationship between cancer diagnosis and the development of clinical scleroderma. A unique nucleolar RNA polymerase III expression pattern has been identified in malignant tissue from these scleroderma patients suggesting that autoantigen expression in the cancer and the autoantibody response are associated. Similar data in inflammatory myositis have illustrated that disease-specific autoantigens may be expressed in cancers and damaged target tissues (muscle) undergoing regeneration.
  
  
  CONCLUSIONS
  These data suggest a model of paraneoplastic autoimmunity in which cross-reactive immune responses may target autoantigens that are expressed in both cancers and diseased autoimmune target tissues.
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ashah32@jhmi.edu
authors.forename: Ami A
authors.initials: AA
authors.lastname: Shah
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
mesh_terms: D001324:Autoantigens; D015551:Autoimmunity; D004948:Esotropia; D006801:Humans; D018448:Models, Immunological; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D010257:Paraneoplastic Syndromes / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D012320:RNA Polymerase III / Q000276:immunology; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000150:complications* / Q000276:immunology
chemical_list: D001324:Autoantigens; D012320:RNA Polymerase III