GLASGOW, SCOTLAND – The presence of specific autoantibodies may help to predict which patients with systemic sclerosis are likely to develop cancer within a few years of their diagnosis, according to the findings of a U.K.-based registry study.
Development of malignancy within 3 years of a diagnosis of scleroderma was positively correlated with the presence of antinuclear antibodies (ANA) directed against RNA polymerase (RNAP) III in more than half (55.3%) of the patients studied (n = 154).
Anticentromere antibodies (ACA) were found in almost a quarter (23.4%) of patients, and 13.6% had antitopoisomerase I (ATA) or anti-Scl70 (antibodies).
Furthermore, patients with anti-RNAP III antibodies had an almost threefold increased risk of cancer compared with patients with ACA (hazard ratio [HR] 2.907; 95% confidence interval [CI] 1.69-4.99, P less than .0001).
"We think that patients who develop scleroderma and cancer can be divided into two different groups," trainee dermatologist Dr. Pia Moinzadeh of the University of Cologne, Germany, said at the annual meeting of the British Society for Rheumatology.
"The first group are those who develop scleroderma and cancer in a very close temporal relationship, and we saw that these patients are most frequently anti-RNA polymerase positive. So scleroderma in these patients can be considered a paraneoplastic disease."
The other group includes patients who develop cancer after a delay of several years from the onset of systemic sclerosis.
Several epidemiological studies have shown an increased risk of malignancy in patients with systemic sclerosis compared with the general population (Br. J. Dermatol. 2010;163:800-6), Dr. Moinzadeh observed.
This includes increases in breast, lung, and hematologic malignancies (Ann. Rheum. Dis. 2003;62:728-31) in 3%-11% of scleroderma cases (South. Med. J. 2008;101:59-62).
"Late onset of scleroderma has been recognized as a significant risk factor for malignancies, and recent reports have also shown a close and, at times, concurrent onset of scleroderma and cancer," Dr. Moinzadeh added (Clin. Rheumatol. 2004;23:516-22; Curr. Opin. Rheumatol. 2011;23:530-5).
The aim of the current study (Rheumatology 2012;51:[suppl. 3]abstract O42) was to determine the risk of cancer and its association with autoantibodies in a large U.K. cohort. Dr. Moinzadeh performed the research while working at the Royal Free Hospital in London with Dr. Voon Ong and colleagues.
Of 2,177 patients with systemic sclerosis, 154 (7.1%) had a history of cancer. The majority (85.1%) of the patients who developed malignancy were female with a median age of 53 years. Almost two-thirds (63.3%) of the patients had limited disease, and 34.4% had diffuse systemic sclerosis. Anti-RNAP, ACA, and Scl70 were detected in 26.6%, 26%, and 18.2% of patients, respectively.
The most common type of cancer was breast cancer (42%), followed by hematologic malignancies (12%), gastrointestinal tumors (11%), gynecologic cancers (11%), and lung cancer (10.4%).
"We found no differences in gender, age, and disease subsets between patients with and without cancer," Dr. Moinzadeh said.
"When we looked closer at the autoantibody subgroups we saw that the overall frequency to develop cancer was significantly higher in the group of patients who were positive for anti-RNA polymerase antibodies compared with the ones which had anticentromere antibodies."
Differences were seen in the frequency of autoantibodies by tumor type. For example, a higher frequency of anti-RNAP antibodies than the other autoantibodies was seen in breast cancer patients, Scl70 was associated with lung cancer, and ACA with gastrointestinal tumors.
While further research is needed to confirm whether anti-RNAP antibodies could be a marker for early cancer in patients with scleroderma, Dr. Moinzadeh noted there were several "red flags" that could perhaps signal if patients were likely to have "paraneoplastic scleroderma."
These red flags included older age (older than 65 years) of scleroderma onset, male gender, contractural arthropathy or palmar fibrosis, lack of ANA antibodies, and no sign of Raynaud’s phenomenon.
"This is a retrospective study, so we are going to do a prospective study in collaboration with Johns Hopkins University School of Medicine," said coinvestigator Dr. Voon Ong, a consultant rheumatologist at the Royal Free Hospital. The collaboration is necessary given that scleroderma is rare, regardless of its association with cancer.
Dr. Moinzadeh and Dr. Ong reported that they had no financial disclosures.