2023: Isolated Anti-Ro52 Antibody Positivity Is Associated with Increased Cancer Risk and Distinct Malignancy Patterns: A Retrospective Cohort Study from a Single Tertiary Center

Background/Purpose: Anti-Ro52 antibodies are frequently detected in patients with systemic autoimmune rheumatic diseases (SARDs). Emerging evidence suggests a potential link between isolated anti-Ro52 positivity and increased malignancy risk.
Our aim was to evaluate: a) the association between anti-Ro52 antibody status (negative, isolated, or combined with other autoantibodies) and malignancy risk; b) whether malignancy types differ according to anti-Ro52 status.

Methods: We conducted a retrospective study of 739 patients who underwent immunoblot testing for autoimmune inflammatory myopathies or systemic sclerosis at a university hospital between November 2017 and October 2023. Patients were stratified by anti-Ro52 status: negative, isolated positivity, or combined with other myositis- or sclerosis-related antibodies. Clinical records were reviewed to confirm SARDs diagnoses using established classification criteria and to identify malignancies through clinical and/or pathological documentation. Associations were analyzed using logistic regression adjusted for age, sex, and SARDs diagnosis.

Results: Malignancy was identified in 61 of 739 patients (8.25%). Anti-Ro52 status distribution: negative (81.4%, n=602), isolated (12.7%, n=94), and combined positivity (5.8%, n=43). In multivariable analysis, older age and isolated Ro52 positivity were independently associated with increased malignancy risk. Each additional year of age increased risk by 5.3% (OR 1.053; 95% CI 1.031–1.076; p< 0.001). Isolated Ro52 positivity conferred a nearly fourfold increased risk versus seronegative patients (OR 3.968; 95% CI 2.049–7.687; p< 0.001). SARDs diagnosis was inversely associated with malignancy (OR 0.426; 95% CI 0.240–0.759; p=0.004). No significant associations were found for sex (OR 0.693; 95% CI 0.392–1.224; p=0.206) or Ro52 positivity combined with other antibodies (OR 1.063; 95% CI 0.297–3.807; p=0.925).

A secondary analysis revealed significant differences in malignancy types by Ro52 status (p=0.001). Ro52-positive patients showed higher frequencies of ovarian, lung, and urothelial cancers, while the Ro52-negative group exhibited a broader, more heterogeneous profile, including colorectal, gastric, and hematological malignancies.

Conclusion: Isolated anti-Ro52 positivity and advancing age are independent predictors of malignancy. The distinct cancer spectrum among Ro52-positive patients suggests the importance of tailored oncologic surveillance in this subgroup.