Aims: To evaluate the biological roles and prognostic significance of the epithelial–mesenchymal transition (EMT)‐mediating transcription factors (TFs) Twist, ZEB1 and Slug in patients with diffuse large B‐cell lymphoma (DLBCL). EMT has been shown to enhance solid tumour metastasis, invasion, and proliferation.
Methods and results: Expression of Twist, ZEB1 and Slug was evaluated immunohistochemically in eight samples from reactive lymphoid tissues and in diagnostic samples from 102 DLBCL patients treated with curative intent with R‐CHOP‐type chemotherapy. ZEB1 and Slug expression correlated with adverse disease presentation. However, cytoplasmic Slug expression was linked to a favourable disease outcome, whereas nuclear expression of ZEB1 indicated an adverse outcome.
Conclusions: This study shows that an EMT‐like process occurs in lymphomas. Of the TFs investigated, ZEB1 seems to be the main one associated with adverse clinical presentation and clinical outcome. Surprisingly, Slug expression in cytoplasm was linked to a favourable prognosis. Further studies are needed to evaluate whether inhibition of ZEB1 could serve as a therapeutic target.
SummaryIn this work, we have studied the biology behind DLBCL central nervous system (CNS) tropism and potential biomarkers for CNS relapse prediction. We show that ITGA10, PTEN, CD44, cadherin-11 and lactoferrin levels are altered in CNS lymphomas.
Central nervous system (CNS) relapse occurs in around 5% of diffuse large B-cell lymphoma (DLBCL) cases. No biomarkers to identify high-risk patients have been discovered. We evaluated the expression of lymphocyte-guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi-square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL.
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