Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B‐cell lymphoma patients with and without rheumatic disease

• Published in: Journal of internal medicine Vol. 278; no. 3; pp. 323 - 332
• Main Authors: Brauner, S., Zhou, W., Backlin, C., Green, T. M., Folkersen, L., Ivanchenko, M., Löfström, B., Xu‐Monette, Z. Y., Young, K. H., Møller Pedersen, L., Boe Møller, M., Sundström, C., Enblad, G., Baecklund, E., Wahren‐Herlenius, M.
• Format: Journal Article
• Language: English
• Published: England 01-09-2015
• Subjects: Aged; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; biomarker; Biomarkers - analysis; Cells, Cultured; Cyclophosphamide - therapeutic use; diffuse large B-cell lymphoma; Doxorubicin - therapeutic use; Female; Humans; Immunohistochemistry; In Vitro Techniques; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - mortality; Male; Medicin och hälsovetenskap; Pathology; Patologi; Prednisolone - therapeutic use; Prednisone - therapeutic use; Prognosis; Real-Time Polymerase Chain Reaction; Rheumatic Diseases - complications; Ribonucleoproteins - analysis; Ro52; TRIM21; Vincristine - therapeutic use; diffuse large B-cell lymphoma; Ro52; biomarker; TRIM21; prognosis
• ISSN: 0954-6820; 1365-2796; 1365-2796
• DOI: 10.1111/joim.12375

Objective
TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B‐cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker.
Materials and methods
TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)‐like regimen, 76 CHOP‐treated and 196 rituximab‐CHOP‐treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with 3H‐thymidine incorporation and propidium iodine staining.
Results
TRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression‐free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes in vitro.
Conclusions
We show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.