Duodenal follicular lymphoma: Comprehensive gene expression analysis with insights into pathogenesis

Abstract

Follicular lymphoma (FL) of the gastrointestinal tract, particularly duodenal follicular lymphoma (DFL), is a rare variant of FL with indolent clinical behavior, and this disease is included in the 2008 World Health Organization classification system. In contrast to nodal follicular lymphoma (NFL), DFL occurs most frequently in the second part of the duodenum, lacks follicular dendritic cell meshworks and has memory B-cell characteristics. However, its molecular pathogenesis is still unclear. In the present study, we examined 10 DFL, 18 NFL and 10 gastric MALT lymphoma samples using gene expression analysis. Quantitative RT-PCR experiments and immunohistochemical analysis for 72 formalin-fixed, paraffin-embedded tissues from an independent series, including 32 DFL, 19 gastric MALT lymphoma and 27 NFL samples, were performed for validation of microarray data. Gene expression profiles of the three lymphoma types were compared using 2918 differentially expressed genes (DEG) and results suggested that DFL shares characteristics of MALT lymphoma. Among these DEG, CCL20 and MAdCAM-1 were upregulated in DFL and MALT but downregulated in NFL. In contrast, protocadherin gamma subfamily genes were upregulated in DFL and NFL. Quantitative RT-PCR and immunohistochemical studies demonstrated concordant results. Double immunofluorescence studies revealed that CCL20 and CCR6 were co-expressed in both DFL and MALT. We hypothesize that increased expression of CCL20 and MAdCAM-1 and co-expression of CCL20 and CCR6 may play an important role in tumorigenesis.

Iodine-131 Rituximab Radioimmunotherapy: Durable Control of Follicular Lymphoma

“…Duodenal FL has different features from nodal FL, including grade 1/2 histology, no marginal zone or plasmacytic differentiation, no reactive germinal centres, and the t(14;18)(q32;q21) positive B-cells do not acquire further karyotypic changes thus they have a low malignant potential [20]. The gene expression profile shows upregulation of Chemokine ligand 20 (CCL20) and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) which is downregulated in nodal FL and may play a role in molecular pathogenesis which is presently unclear [21].…”

Recurrent mutations and targeted therapy in FL

“…3 In 1948, 2 French physicians, Jean Bernard and Jean-Pierre Soulier, first reported a severe bleeding disorder associated with thrombocytopenia and giant platelets, later shown to be characterized by decreased ristocetin-induced platelet agglutination. 3,4 To date, 45, 39, and 28 variants in GP1BA, GP1BB, and GP9, respectively, have been identified in the BSS. 4 GP5 variants have not been implicated in the BSS.…”

“…3,4 To date, 45, 39, and 28 variants in GP1BA, GP1BB, and GP9, respectively, have been identified in the BSS. 4 GP5 variants have not been implicated in the BSS. In contrast to these loss-of-function variants, some GP1BA variants have conferred an increase in affinity of the platelet complex for VWF, resulting in the platelet-type vWD associated with a secondary decrease in plasma high molecular weight VWF multimers.…”

“…These include pediatric-type FL and primary intestinal FL, each of which has been found to be biologically distinct from typical nodal FL cases. 3,4 The t(14;18) is present in the majority of FLs and serves as a defining molecular feature. This translocation, which results in constitutive expression of the antiapoptotic BCL2 protein, appears to be an early genetic event that alone is insufficient to result in lymphomagenesis.…”

A multicenter survey of enteroscopy for the diagnosis of intestinal follicular lymphoma

“…A subset of the 110 patients examined also participated in a number of our previous studies (4,6,(12)(13)(14)(15)(16)(17)(18)(19).…”