Duodenal Follicular Lymphoma Shares Characteristics of MALT Lymphoma: Comprehensive Gene Expression Analysis with Insights into Pathogenesis
Katsuyoshi Takata, Motohiko Taniho, Daisuke Ennishi, Akira Tari, Yasuharu Sato, Hiroyuki Okada, Naoe Goto, Yoshinobu Maeda, Randy D Gascoyne, Tadashi Yoshino. Okayama University, Okayama, Japan; DNA Chip Research Inc., Yokohama, Japan; BC Cancer Agency & BC Cancer Research Centre, Vancouver, Canada; Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan; Okayama University Hospital, Okayama, Japan; Gifu University, Gifu, Japan
Background: Follicular lymphoma of the gastrointestinal tract, especially duodenal follicular lymphoma (DFL), is a rare variant of follicular lymphoma (FL) included in the 2008 WHO classification. We previously reported that DFL occurs most frequently in the 2nd part of the duodenum, lacks follicular dendritic cell meshworks and has very indolent clinical behavior compared to nodal FL (NFL). We sought to examine its pathogenesis using gene expression profiling (GEP).
Design: Total RNA was extracted from the following fresh frozen samples: 10 DFL, 18 NFL, 10 gastric MALT lymphomas, 5 normal duodenal mucosa, 8 nodal reactive lymphoid hyperplasia (RLH) and 4 normal gastric mucosa. Labeled cRNAs were synthesized and then hybridized to Whole Human Genome Agilent 8 X 60K commercial oligo-DNA microarrays (Agilent Technologies). After subtracting background noise, the intensity data were normalized using a75 percentile normalization. Differentially expressed genes (DEGs) for each lymphoma were then selected as compared with normal tissue data. Hierarchical clustering was done for GEP.
Results: GEP of three lymphoma types was compared using 2,918 DEGs (T-test corrected p-value < 0.05 and 2-fold up/down) and suggested that DFL shares characteristics of both MALT lymphoma and NFL, with more similarities to MALT lymphoma. We previously found that cytokines, chemokines and adhesion molecules were involved in tumorigenesis. Among these molecules, CCL20 and MAdCAM-1 were up-regulated in DFL and MALT but down-regulated in NFL based on DEGs. Quantitative RT-PCR and immunohistochemical studies demonstrated concordant results.
Conclusions: Our results suggest that DFL shares biological characteristics of both MALT lymphoma and NFL, but is more similar to MALT lymphoma. Increased expression of CCL20 and MAdCAM-1 distinguish DFL and MALT lymphoma from NFL and may play an important role for tumor localization within the duodenum and further suggest that an inflammatory background and probable antigen stimulation underlie tumorigenesis.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 234, Wednesday Afternoon