Chemokine receptors in gastric MALT lymphoma: Loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma

Deutsch, Alexander JA, Steinbauer, Elisabeth, Hofmann, Nicole A, Strunk, Dirk, Gerlza, Tanja, Beham-Schmid, Christine, Schaider, Helmut and Neumeister, Peter (2013) Chemokine receptors in gastric MALT lymphoma: Loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma. Modern Pathology, 26 2: 182-194. doi:10.1038/modpathol.2012.134


Author Deutsch, Alexander JA
Steinbauer, Elisabeth
Hofmann, Nicole A
Strunk, Dirk
Gerlza, Tanja
Beham-Schmid, Christine
Schaider, Helmut
Neumeister, Peter
Title Chemokine receptors in gastric MALT lymphoma: Loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma
Journal name Modern Pathology   Check publisher's open access policy
ISSN 0893-3952
1530-0285
Publication date 2013-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1038/modpathol.2012.134
Volume 26
Issue 2
Start page 182
End page 194
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Chemokine receptors have a crucial role in the development and progression of lymphoid neoplasms. To determine the chemokine receptor expression profile in gastric mucosa-associated lymphoid tissue (MALT) lymphoma, we performed an expression analysis of 19 chemokine receptors at mRNA levels by using real-time RT-PCR, as well as of five chemokine receptors-CCR8, CCR9, CXCR4, CXCR6 and CXCR7-by immunohistochemistry on human tissue samples of Helicobacter pylori-associated gastritis, gastric MALT lymphoma and gastric extranodal diffuse large B-cell lymphoma originating from MALT lymphoma (transformed MALT lymphoma). Following malignant transformation from H. pylori-associated gastritis to MALT lymphoma, an upregulation of CCR7, CXCR3 and CXCR7, and a loss of CXCR4 were detected. The transformation of gastric MALT lymphomas to gastric extranodal diffuse large B-cell lymphoma was accompanied by upregulation of CCR1, CCR5, CCR7, CCR8, CCR9, CXCR3, CXCR6, CXCR7 and XCR1. Remarkably, CXCR4 expression was exclusively found in nodal marginal B-cell lymphomas and nodal diffuse large B-cell lymphomas but not at extranodal manifestation sites, ie, in gastric MALT lymphomas or gastric extranodal diffuse large B-cell lymphomas. Furthermore, the incidence of bone marrow infiltration (16/51 with bone marrow involvement vs 35/51 with bone marrow involvement; Spearman ρ=0467 P<0.001) positively correlated with CXCR4 expression. CXCL12, the ligand of CXCR4 and CXCR7, was expressed by epithelial, endothelial and inflammatory cells, MALT lymphoma cells and was most strongly expressed by extranodal diffuse large B-cell lymphoma cells, suggesting at least in part an autocrine signaling pathway. Our data indicate that CXCR4 expression is associated with nodal manifestation and a more advanced stage of lymphomas and hence, might serve as useful clinical prognostic marker.
Keyword Chemokine receptor
Chemokines
CXCR4
CXCR7
MALT lymphoma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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