Antinuclear Antibodies With a Homogeneous and Speckled Immunofluorescence Pattern Are Associated With Lack of Cancer While Those With a Nucleolar Pattern With the Presence of Cancer

Abstract

Background: Different antinuclear antibody (ANA) patterns have been associated with the presence of cancer, while other are typically seen in autoimmune diseases. This study aims to investigate the association between ANA and cancer, focusing on patients with ANA with a nucleolar indirect immunofluorescence (IIF) pattern. Materials and Methods: ANA patterns and positivity of antibodies against nuclear antigens (NA), in particular those responsible for a nucleolar ANA pattern and/or associated with systemic sclerosis (CENP-A/B, fibrillarin, Ku, NOR-90, PM/Scl-100, PM/Scl-75, RNAP-III, Scl-70, Ro52/TRIM21, and Th/To) were analyzed and correlated to an internal database of patients with cancer. Results: The study included 15,728 patients who had an ANA analysis, 386 patients who had immunodot analysis for antibody/ies against/to specific NA and 15,701 patients diagnosed with cancer. The presence of ANA with a nucleolar pattern showed an increased relative risk (RR 1.5, 95%CI 1.03-2.3) for an associated cancer. Anti-Scl70 and anti-RNAP-III were associated with cancer in 15 and 14%, respectively. The presence of ANA with a homogeneous & speckled (HS) pattern was significantly associated with the absence of cancer (p < 0.01). Patients with a HS pattern were found to have a lower relative risk (RR 0.7, 95%CI 0.5-0.9) of having cancer compared to those with other patterns. Conclusions: Larger studies are needed to investigate which particular antibody/ies against/to specific NA is responsible for the association between nucleolar ANA and cancer, but anti-Scl70 and anti-RNAP-III, which is frequently associated with the presence of anti-RNAP-I, are good candidates to explain this association. Patients with a nucleolar pattern might be considered for cancer screening, in particular if they have anti-Scl70 and anti-RNAP-III antibodies.

Clinical and Molecular Features of Anti-CENP-B Autoantibodies

“…Finally, Gauderon et al recently conducted a retrospective study of cancer risk in patients with autoantibodies detected by immunofluorescence [35]. In addition to an increased incidence of cancer in patients with anti-RPC1, their findings also support the concept of high-and low-risk subtypes within autoimmune diseases.…”

“…In addition to an increased incidence of cancer in patients with anti-RPC1, their findings also support the concept of high-and low-risk subtypes within autoimmune diseases. Interestingly, the ACA pattern had the lowest relative cancer risk of any pattern, although the study was underpowered to reach statistical significance [35].…”

“…In contrast to classical paraneoplastic diseases, there appears to be a low incidence of cancer in ACA-positive scleroderma. In cases that do develop, scleroderma symptoms seem largely uncoupled from cancer diagnosis [25,30,35]. Nonetheless, in stand-alone cancer cases, it does appear that malignancy can be a source of autoantigens.…”

Antinuclear Antibodies With a Nucleolar Pattern Are Associated With a Significant Reduction in the Overall Survival of Patients With Leukemia: A Retrospective Cohort Study

“…Additionally, the significance of the ANA patterns is ignored in clinical practice and research. A recent study showed that the presence of ANAs with a nucleolar pattern was associated with an increased relative risk of cancer (15). Furthermore, the significance of ANA patterns, especially the cell-cycle related ANAs, was emphasized in carcinoma (31,32).…”

“…Furthermore, different ANA patterns have been associated with the presence of cancer. ANAs with a homogeneous and speckled immunofluorescence pattern are associated with lack of cancer, while those with a nucleolar pattern are associated with the presence of cancer (15). The positivity for the anti-centromere antibody is reported as a statistically significant risk factor for cancer (16).…”