ABSTRACT
ABSTRACT Objectives: To investigate the protein expression of the epithelial-mesenchymal transition-inducing transcription factors (TFs) Twist, ZEB1 and Slug in peripheral T-cell lymphomas (PTCL) and their correlation with clinical parameters. Methods: The expression of these TFs was studied in 53 diagnostic biopsy specimens of several different PTCL subtypes with immunohistochemistry. Patient data were retrospectively collected from patient records and a statistical analysis was performed. Results: All three TFs were widely expressed. ZEB1 and Slug had correlations with clinical outcome. In all PTCL cases, high nuclear ZEB1 percentage correlated with a favorable progression-free survival (PFS) (3-year PFS: 70% vs. 34%; P = 0.010) and strong nuclear Slug intensity correlated with an unfavorable PFS (3-year PFS: 17% vs. 62%; P = 0.036). Discussion: The correlations between PFS and ZEB1 or Slug protein expression have not previously been established in PTCLs. The impact of ZEB1 and Slug expression on prognosis differed from our findings in DLBCL and the impact of ZEB1 expression was in line with current studies on mycosis fungoides and sézary syndrome. The findings may be explained by the roles these TFs play in hematopoiesis. Conclusion: ZEB1 and Slug may have potential clinical value for evaluating prognosis in PTCLs. The study size was small and heterogenous, and larger studies are warranted.
Subject(s)
Lymphoma, T-Cell, Peripheral/genetics , Snail Family Transcription Factors/metabolism , Twist-Related Protein 1/metabolism , Zinc Finger E-box-Binding Homeobox 1/metabolism , Female , Humans , Male , Middle Aged , PrognosisABSTRACT
Central nervous system (CNS) relapse is a devastating complication that occurs in about 5% of diffuse large B-cell lymphoma (DLBCL) patients. Currently, there are no predictive biological markers. We wanted to study potential biomarkers of CNS tropism that play a role in adhesion, migration and/or in the regulation of inflammatory responses. The expression levels of ITGA10, CD44, PTEN, cadherin-11, CDH12, N-cadherin, P-cadherin, lactoferrin and E-cadherin were studied with IHC and IEM. GEP was performed to see whether found expressional changes are regulated at DNA/RNA level. IHC included 96 samples of primary CNS lymphoma (PCNSL), secondary CNS lymphoma (sCNSL) and systemic DLBCL (sDLBCL). IEM included two PCNSL, one sCNSL, one sDLBCL and one reactive lymph node samples. GEP was performed on two DLBCL samples, one with and one without CNS relapse. CNS disease was associated with enhanced expression of cytoplasmic and membranous ITGA10 and nuclear PTEN (P < 0.0005, P = 0.002, P = 0.024, respectively). sCNSL presented decreased membranous CD44 and nuclear and cytoplasmic cadherin-11 expressions (P = 0.001, P = 0.006, P = 0.048, respectively). In PCNSL lactoferrin expression was upregulated (P < 0.0005). IEM results were mainly supportive of the IHC results. In GEP CD44, cadherin-11, lactoferrin and E-cadherin were under-expressed in CNS disease. Our results are in line with previous studies, where gene expressions in extracellular matrix and adhesion-related pathways are altered in CNS lymphoma. This study gives new information on the DLBCL CNS tropism. If further verified, these markers might become useful in predicting CNS relapses.
Subject(s)
Cadherins/genetics , Central Nervous System Diseases/genetics , Hyaluronan Receptors/genetics , Integrin alpha Chains/genetics , Lactoferrin/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , PTEN Phosphohydrolase/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Cadherins/biosynthesis , Central Nervous System/pathology , Central Nervous System Diseases/etiology , Central Nervous System Diseases/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Hyaluronan Receptors/biosynthesis , Integrin alpha Chains/biosynthesis , Lactoferrin/biosynthesis , Lymph Nodes/metabolism , Lymph Nodes/pathology , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , PTEN Phosphohydrolase/biosynthesisABSTRACT
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.
