Overexpression of caspase recruitment domain (CARD) membrane-associated guanylate kinase 1 (CARMA1) and CARD9 in primary gastric B-cell lymphoma
Overexpression of caspase recruitment domain (CARD) membrane-associated guanylate kinase 1 (CARMA1) and CARD9 in primary gastric B-cell lymphoma
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作者：
Nakamura, S;Nakamura, S;Iida, M
背景尽管caspase募集结构域（CARD）膜相关鸟苷酸激酶（MAGUK）蛋白I（CARMAI）和CARD 9在淋巴细胞活化中起重要作用，但CARMAI和CARD 9在胃粘膜相关淋巴组织（N4 ALT）淋巴瘤发病中的意义尚待阐明。应用逆转录-聚合酶链反应（RT-PCR）技术检测65例原发性胃B细胞淋巴瘤组织中CARMA 1、CARD 9、Bcl 10及凋亡抑制因子2（API 2）-MALT 1嵌合体mRNA的表达水平（43例低度MALT淋巴瘤患者，16例N4ALT淋巴瘤+弥漫性大B细胞淋巴瘤[DLBL]患者，和6例DLBL无MALT淋巴瘤）和18例慢性胃炎患者的组织标本。采用免疫组化法检测30例淋巴瘤组织中CARMA 1和BCL 10的表达水平。在55%的淋巴瘤患者中检测到CARMA 1 mRNA，而在慢性胃炎患者中仅检测到17%。CARD 9、Bcl 10和AP 12 MALTI嵌合体转录本在淋巴瘤患者中的阳性率分别为48%、98%和8%，而在慢性胃炎患者的任何标本中均未检测到这3种分子。CARMA 1和CARD 9的表达在幽门螺杆菌阴性患者（分别为100%和86%）、API 2-MALT 1嵌合转录阳性患者（分别为100%和100%）以及对H.幽门螺杆菌根除（分别为76%和71%）。此外，CARMA 1在DLBL无MALT淋巴瘤患者中的阳性表达率（100%）高于N4ALT淋巴瘤患者（51%）。CARMA 1蛋白表达与CARMA 1 mRNA表达及核BCL 10表达呈显著相关。CARMA 1和CARD 9的过表达可能与胃B细胞淋巴瘤的发生或进展相关，特别是在发病机制与H.幽门。
BACKGROUND. Although caspase recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein I (CARMAI) and CARD9 play important roles in lymphocyte activation, the significance of CARMAI and CARD9 in the pathogenesis of gastric mucosa-associated lymphoid tissue (N4ALT) 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 N4ALT 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 AP12MALTI 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 N4ALT 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.