OBJECTIVE: This study was undertaken to examine the temporal relationship between scleroderma development and malignancy, and to evaluate whether this differs by autoantibody status among affected patients. METHODS: Study participants had a diagnosis of scleroderma, a diagnosis of cancer, cancer, an available serum sample, and a cancer pathology specimen. Sera were tested for autoantibodies against topoisomerase I, centromere, and RNA polymerase I/III by immunoprecipitation and/or enzyme-linked immunosorbent assay. Clinical and demographic characteristics were compared across autoantibody categories. Expression of RNA polymerases I and III was evaluated by immunohistochemistry using cancerous tissue from patients with anti-RNA polymerase antibodies. RESULTS: Twenty-three patients were enrolled. Six patients tested positive for anti-RNA polymerase I/III, 5 for anti-topoisomerase I, and 8 for anticentromere, and 4 were not positive for any of these antigens. The median duration of scleroderma at cancer diagnosis differed significantly between groups (-1.2 years in the anti-RNA polymerase I/III group, +13.4 years in the anti-topoisomerase I group, +11.1 years in the anticentromere group, and +2.3 years in the group that was negative for all antigens tested) (P = 0.027). RNA polymerase III demonstrated a robust nucleolar staining pattern in 4 of 5 available tumors from patients with antibodies to RNA polymerase I/III. In contrast, nucleolar RNA polymerase III staining was not detected in any of 4 examined tumors from the RNA polymerase antibody-negative group (P = 0.048). CONCLUSION: Our findings indicate that there is a close temporal relationship between the onset of cancer and scleroderma in patients with antibodies to RNA polymerase I/III, which is distinct from scleroderma patients with other autoantibody specificities. In this study, autoantibody response and tumor antigen expression are associated. We propose that malignancy may initiate the scleroderma-specific immune response and drive disease in a subset of scleroderma patients.
OBJECTIVE: This study was undertaken to examine the temporal relationship between scleroderma development and malignancy, and to evaluate whether this differs by autoantibody status among affected patients. METHODS: Study participants had a diagnosis of scleroderma, a diagnosis of cancer, cancer, an available serum sample, and a cancer pathology specimen. Sera were tested for autoantibodies against topoisomerase I, centromere, and RNA polymerase I/III by immunoprecipitation and/or enzyme-linked immunosorbent assay. Clinical and demographic characteristics were compared across autoantibody categories. Expression of RNA polymerases I and III was evaluated by immunohistochemistry using cancerous tissue from patients with anti-RNA polymerase antibodies. RESULTS: Twenty-three patients were enrolled. Six patients tested positive for anti-RNA polymerase I/III, 5 for anti-topoisomerase I, and 8 for anticentromere, and 4 were not positive for any of these antigens. The median duration of scleroderma at cancer diagnosis differed significantly between groups (-1.2 years in the anti-RNA polymerase I/III group, +13.4 years in the anti-topoisomerase I group, +11.1 years in the anticentromere group, and +2.3 years in the group that was negative for all antigens tested) (P = 0.027). RNA polymerase III demonstrated a robust nucleolar staining pattern in 4 of 5 available tumors from patients with antibodies to RNA polymerase I/III. In contrast, nucleolar RNA polymerase III staining was not detected in any of 4 examined tumors from the RNA polymerase antibody-negative group (P = 0.048). CONCLUSION: Our findings indicate that there is a close temporal relationship between the onset of cancer and scleroderma in patients with antibodies to RNA polymerase I/III, which is distinct from sclerodermapatients with other autoantibody specificities. In this study, autoantibody response and tumor antigen expression are associated. We propose that malignancy may initiate the scleroderma-specific immune response and drive disease in a subset of sclerodermapatients.
Authors: S Bernatsky; J F Boivin; L Joseph; R Rajan; A Zoma; S Manzi; E Ginzler; M Urowitz; D Gladman; P R Fortin; M Petri; S Edworthy; S Barr; C Gordon; S C Bae; J Sibley; D Isenberg; A Rahman; C Aranow; M A Dooley; K Steinsson; O Nived; G Sturfelt; G Alarcón; J L Senécal; M Zummer; J Hanly; S Ensworth; J Pope; H El-Gabalawy; T McCarthy; Y St Pierre; R Ramsey-Goldman; A Clarke Journal: Arthritis Rheum Date: 2005-05
Authors: A C Gelber; S R Pillemer; B J Baum; F M Wigley; L K Hummers; S Morris; A Rosen; L Casciola-Rosen Journal: Ann Rheum Dis Date: 2006-01-13 Impact factor: 19.103
Authors: T A Medsger; A J Silman; V D Steen; C M Black; A Akesson; P A Bacon; C A Harris; S Jablonska; M I Jayson; S A Jimenez; T Krieg; E C Leroy; P J Maddison; M L Russell; R K Schachter; F A Wollheim; H Zacharaie Journal: J Rheumatol Date: 1999-10 Impact factor: 4.666
Authors: Ami A Shah; George Xu; Antony Rosen; Laura K Hummers; Fredrick M Wigley; Stephen J Elledge; Livia Casciola-Rosen Journal: Arthritis Rheumatol Date: 2017-06 Impact factor: 10.995