Drs. Wigley and Casciola-Rosen contributed equally to this work.
Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies
Article first published online: 6 MAY 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 9, pages 2787–2795, September 2010
How to Cite
Shah, A. A., Rosen, A., Hummers, L., Wigley, F. and Casciola-Rosen, L. (2010), Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis & Rheumatism, 62: 2787–2795. doi: 10.1002/art.27549
- Issue published online: 31 AUG 2010
- Article first published online: 6 MAY 2010
- Manuscript Accepted: 27 APR 2010
- Manuscript Received: 17 NOV 2009
- Scleroderma Research Foundation
- Stabler Foundation
- American College of Rheumatology Research and Education Foundation Clinical Investigator Fellowship
- Karen Brown Scleroderma Foundation
- NIH. Grant Numbers: P30-AR-058885, R37-DE-12354, 1K23-AR-052742, 1P50-HL-084946-01, R01-AR-044684
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.
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.
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).
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.