Overexpression of caspase recruitment domain (CARD) membrane-associated guanylate kinase 1 (CARMA1) and CARD9 in primary gastric B-cell lymphoma.
BACKGROUND
Although caspase recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) and CARD9 play important roles in lymphocyte activation, the significance of CARMA1 and CARD9 in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma remains to be elucidated.


METHODS
By using reverse transcription-polymerase chain reaction analysis, the expression levels of mRNA of CARMA1, CARD9, Bcl10, and the apoptosis inhibitor 2 (API2)-MALT1 chimeric transcript were determined in tissue specimens from 65 patients with primary gastric B-cell lymphoma (43 patients with low-grade MALT lymphoma, 16 patients with MALT lymphoma plus diffuse large B-cell lymphoma [DLBL], and 6 patients with DLBL without MALT lymphoma) and in tissue specimens from 18 patients with chronic gastritis. The expression levels of CARMA1 and BCL10 were examined immunohistochemically in 30 patients with lymphoma.


RESULTS
CARMA1 mRNA was detected in 55% of lymphoma patients but in only 17% of chronic gastritis patients. The positive rates for CARD9, Bcl10, and API2-MALT1 chimeric transcript in the lymphoma patients were 48%, 98%, and 8%, respectively, whereas the 3 molecules were not detected in any specimens from patients with chronic gastritis. The expression of CARMA1 and CARD9 was frequent in the Helicobacter pylori-negative patients (100% and 86%, respectively), in the API2-MALT1 chimeric transcript-positive patients (100% and 100%, respectively), and in the specimens from patients who did not respond to H. pylori eradication (76% and 71%, respectively). In addition, CARMA1 expression was positive more frequently in patients of DLBL without MALT lymphoma (100%) than in patients of MALT lymphoma (51%). CARMA1 protein expression was correlated significantly with the expression of CARMA1 mRNA and also with the expression of nuclear BCL10.


CONCLUSIONS
The overexpression of CARMA1 and CARD9 presumably is associated with the development or progression of gastric B-cell lymphoma, especially among patients who have disease in which the pathogenesis is not related to H. pylori.
Nakamura
Shigeo
S
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan.
Nakamura
Shotaro
S
Matsumoto
Takayuki
T
Yada
Shinichiro
S
Hirahashi
Minako
M
Suekane
Hiroshi
H
Yao
Takashi
T
Goda
Kenichi
K
Iida
Mitsuo
M
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins; D005260:Female; D005756:Gastritis / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018442:Lymphoma, B-Cell, Marginal Zone / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000209:etiology* / Q000378:metabolism
C415943:API2-MALT1 fusion protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C426242:CARD11 protein, human; D006162:Guanylate Cyclase