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Reduced expression of TRIM 21/Ro52 predicts poor prognosis in diffuse large B‐cell lymphoma patients with and without rheumatic disease
Author(s) -
Brauner S.,
Zhou W.,
Backlin C.,
Green T. M.,
Folkersen L.,
Ivanchenko M.,
Löfström B.,
XuMonette Z. Y.,
Young K. H.,
Møller Pedersen L.,
Boe Møller M.,
Sundström C.,
Enblad G.,
Baecklund E.,
WahrenHerlenius M.
Publication year - 2015
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12375
Subject(s) - medicine , lymphoma , vincristine , trim , chop , diffuse large b cell lymphoma , pathology , cancer research , immunology , cyclophosphamide , oncology , chemotherapy , computer science , operating system
Objective TRIM 21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM 21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM 21 in patients with diffuse large B‐cell lymphoma ( DLBCL ) and its potential usefulness as a prognostic biomarker. Materials and methods TRIM 21 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. TRIM 21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with 3 H‐thymidine incorporation and propidium iodine staining. Results TRIM 21 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 TRIM 21 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 TRIM 21 expression and proliferation of leucocytes in vitro . Conclusions We show that loss of TRIM 21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM 21 expression is associated with better prognosis in patients with DLBCL . Based on our findings, we suggest that TRIM 21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.