Open AccessClose temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies
Author(s) -
Shah Ami A.,
Rosen Antony,
Hummers Laura,
Wigley Fredrick,
CasciolaRosen Livia
Publication year - 2010
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.27549
Subject(s) - autoantibody , cancer , polymerase , scleroderma (fungus) , rna polymerase iii , malignancy , polymerase chain reaction , rna , antibody , biology , medicine , microbiology and biotechnology , pathology , rna polymerase , immunology , dna , gene , genetics , inoculation
Abstract 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.