Expression of CARD11 (CARMA1) and efficacy of non-surgical treatment in gastric MALT lymphoma

虽然caspase募集结构域(CARD)-膜相关鸟苷酸激酶（MAGUK）蛋白1 （CARMA1/CARD11）和CARD9在淋巴细胞活化中发挥重要作用，但CARMA1和CARD9在胃粘膜相关淋巴组织（MALT）淋巴瘤发病机制中的意义仍有待阐明。本研究采用逆转录-聚合酶链反应，对65例原发性胃b细胞淋巴瘤（低级别MALT淋巴瘤43例，MALT淋巴瘤合并弥漫性大b细胞淋巴瘤16例，无MALT淋巴瘤的DLBCL 6例）和18例慢性胃炎组织标本中CARMA1、CARD9、BCL10和API2-MALT1嵌合转录物mRNA的表达进行了研究。用免疫组织化学方法检测了30例淋巴瘤中CARMA1和BCL10蛋白的表达。结果，在55%的淋巴瘤病例中检测到CARMA1 mRNA，而在慢性胃炎病例中仅检测到17%。CARD9、BCL10和API2-MALT1嵌合转录物在淋巴瘤病例中的阳性率分别为48%、98%和8%，而这三种分子在慢性胃炎病例中均未检出。CARMA1和CARD9在幽门螺杆菌阴性病例（100%和86%）、API2-MALT1嵌合转录物阳性病例（100%和100%）和幽门螺杆菌根除无效病例（76%和71%）中表达频率较高。此外，CARMA1在无MALT淋巴瘤的DLBCL中阳性表达（100%）高于MALT淋巴瘤（51%）。CARMA1蛋白表达与CARMA1 mRNA表达及核BCL10表达显著相关。综上所述，CARMA1和CARD9的过表达被认为与胃b细胞淋巴瘤的发生或进展有关，特别是对于那些幽门螺杆菌与发病机制无关的病例。

While caspase recruitment domain (CARD)-membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1/CARD11) 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 still remains to be elucidated. In the current research, we investigated the expression of mRNA of CARMA1, CARD9, BCL10 and the API2-MALT1 chimeric transcript in tissue specimens from 65 cases of primary gastric B-cell lymphoma (43 cases of low-grade MALT lymphoma, 16 MALT lymphoma plus diffuse large B-cell lymphoma [DLBCL] and 6 DLBCL without MALT lymphoma) and 18 cases of chronic gastritis, using the reverse transcription-polymerase chain reaction. The expressions of CARMA1 and BCL10 proteins were also examined immunohistochemically in 30 cases of lymphoma. As a result, CARMA1 mRNA was detected in 55% of the lymphoma cases, but in only 17% of the chronic gastritis cases. The positive rates of CARD9,BCL10 and API2-MALT1 chimeric transcript in the lymphoma cases were 48%,98%, and 8%, respectively, while these three molecules were not detected in any cases with chronic gastritis. The expression of CARMA1 and CARD9 was frequent in the H.pylori negative cases (100% and 86%), in the API2-MALT1 chimeric transcript positive cases (100% and 100%), and in the cases not responding to H.pylori eradication (76% and 71%). In addition, the CARMA1 expression was more frequently positive in DLBCL without MALT lymphoma (100%) than in MALT lymphomas (51%). CARMA1 protein expression significantly correlated to the expression of CARMA1 mRNA and also to nuclear BCL10 expression. In conclusion, overexpression of CARMA1 and CARD9 is presumed to be associated with the development or progression of gastric B-cell lymphoma, especially for those cases in which H.pylori is unrelated to the pathogenesis.