Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy

AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosaassociated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy.METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy,the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissuefluorescence in situ hybridization (FISH), using chromosomespecific α-satellite DNA probes for chromosomes 3,7,12,and 18 and YAC clones for t(11;18)(q21;q21).RESULTS: Seven of the 13 patients had complete regression(CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients.CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

Expression of CD86 and increased infiltration of NK cells are associated with Helicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

AIM: A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori(H pylori)-dependent. However,unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori-specific intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 (B7.2) and the infiltration of CD56 (+) natural killer (NK) cells can be useful markers to predict Hpylori-dependent status of high-grade gastric MALT lymphoma.METHODS: Lymphoma biopsies from 26 patients who had participated in a prospective study of H pylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade Ⅱ or less after H pylorieradication were classified as H pyloridependent; others were classified as H pylori-independent.The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry.RESULTS: There were 16 H pylori-dependent and 10H pylori-independent cases. CD86 expression was detected in 11 (68.8%) of 16 Hpyiori-dependent cases but in none of 10 Hpylori-independent cases (P = 0.001).H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 (+) NK cells than H pylori-independent cases (2.8±1.4% vs 1.1±0.8%; P = 0.003). CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 (+)NK cells compared to CD86-negative cases (2.9±1.1% vs1.4±1.3%; P= 0.005).CONCLUSION: These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with H pylori-dependent state of early-stage high-grade gastric MALT lymphomas.

Complete or partial trisomy 3 in gastro-intestinal MALT lymphomas co-occurs with aberrations at 18q21 and correlates with advanced disease stage:A study on 25 cases

TO THE EDITOR Taji et al.[1] have reported in their study on 13 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphomas an aggressive tumor course in trisomy 3 positive cases. The authors analyzed only stage I patients with classical low-grade marginal zone lymphoma of the MALT type and detected the trisomy 3 using an alphasatellite DNA probe directed to the centromere. Their data support the observation that trisomy 3 is the most frequent cytogenetic aberration in MALT lymphomas[2,3].

The clinical significance of CD97, NF-kB and COX-2 ingastric MALT lymphomas

Background and Objectives: Increased expression of the CD97, nuclear factor-kB (NF-kB) and cyclooxygenase-2 (COX-2) has been found to play an important role in development of many cancers, including gastric neoplasm. However, the expression and biological behavior of CD97, NF-kB and COX-2 in gastric MALT (mucosa-associated lymphoid tissue) lymphoma has not been well investigated. Methods: The expressions of CD97, COX-2 and NF-kB in 47 cases of gastric MALT lymphoma were detected immunohistochemically, and the relevance between their expressions and the biological behavior was analyzed retrospectively. Results: 1) The expressions of CD97, NF-kB and COX-2 were 87.2%, 36.2% and 48.9%, respectively;2) The difference of CD97 expression between depth of invasion limited in mucosa and submucosa and beyond muscularis propria was significant (100.0% vs. 71.4%, P < 0.01). Moreover, the expression of nuclear CD97 between stage IIE, III, IV and stage I patients showed significant difference (96.4% vs. 73.7%, P < 0.05);3) The expression of NF-kB was significantly correlated with tumor size, depth of invasion and stage;4) The expression of COX-2 was significantly correlated with Helicobacter pylori infection, clinical stage, depth of invasion and tumor size (P < 0.05). Conclusions: Expressions of CD97, NF-κB and COX-2 were correlated with tumor invasion and metastasis in gastric MALT lymphoma.

T(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas are heterogeneous with respect to the V_H gene mutation status

<Abstract>AIM: To investigate how t(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas relate to other marginal zone lymphomas with respect to the somatic mutation pattern of the VH genes and the expression of the marker CD27. METHODS: The VH gene of 7 t(11;18)(q21;q21)- positive gastrointestinal MALT lymphomas was amplif iedby PCR using family specif ic VH primers and a consensus JH primer. PCR products were sequenced and mutation analysis of the CDR and the FR regions was performed. All cases were immunostained for CD27. RESULTS: One case showed unmutated VH genes while the others showed mutated VH genes with mutation frequencies ranging from 1.3 to 14.7% and with evidence of antigen selection in 2 cases. These data suggest that the translocation t(11;18)(q21;q21) can target either B-cells at different stages of differentiation or naive B-cells that retain the capacity to differentiate upon antigen stimulation. All cases but one displayed weak to strong CD27 expression which did not correlate with the VH gene mutation status. CONCLUSION: t(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas are heterogeneous with respect to the VH mutation status and CD27 is not a marker of somatically mutated B-cells.

Massive bleeding in small intestinal mucosa-associated lymphoid tissue lymphoma associated with COVID-19 infection:a case report

The increased risk of mucosa-associated lymphoid tissue(MALT)lymphoma is closely associated with chronic antigenic stimulation,with infection being the most common cause of recurrence.Lesions are usually associated with the gastrointestinal tract,and the involvement of small intestinal is rare.Recent studies have established a close relationship between novel coronavirus 2019(COVID-19)and the occurrence and progression of various diseases.This article presents a rare case of a small intestinal MALT lymphoma.The patient was initially admitted with COVID-19 pneumonia and subsequently developed gastrointestinal bleeding during hospitalization.Medical and endoscopic treatments were ineffective,and an emergency exploratory laparotomy was performed.The affected segment of the small intestine was excised,and a pathological biopsy confirmed the diagnosis of MALT lymphoma.This case underscores the significance of raising clinical awareness of this condition among health care professionals.

涎腺原发性MALT淋巴瘤5例临床病理分析

目的 探讨涎腺原发性结外边缘区黏膜相关淋巴组织(MALT)淋巴瘤的临床病理特征。方法 回顾性分析5例涎腺MALT淋巴瘤的临床病理资料,并复习相关文献。结果 5例患者中,女性3例,男性2例,发病年龄32~71岁,肿块位于单侧腮腺/颌下腺。肿瘤细胞主要由多种形态的肿瘤性边缘区B细胞构成,弥漫或结节状浸润生长,见“滤泡植入”、“淋巴上皮病变”伴导管内聚集生长、伴导管上皮周围基底膜样嗜酸性物质增多,见脉管、神经侵犯。肿瘤细胞B细胞相关抗原弥漫阳性,CD5、CD23、Cyclin D1均阴性,Ki-67增殖指数10%~30%。随访8~97个月,5例均未行放化疗,3例无复发,1例继发右上腭MALT淋巴瘤,1例死亡。结论 涎腺MALT淋巴瘤具有一定的形态学特征,呈B细胞免疫表型且无其他小B细胞淋巴瘤的表型特征。本病呈惰性进程,预后一般较好,可累及周围淋巴结及其他涎腺腺体,有复发和远处播散的风险,需要长期密切随访。

THE CLINICAL PATHOLOGY AND DNA PLOIDY OF GASTRICMUCOSA ASSOCIATED LYMPHOID TISSUE (MALT)LYMPHOMA INFILTRATING THE LEIOMYOMASOF THE UTERUS

Objective: To investigate the clinicopathology and DNA ploidy of gastric mucosa associated lymphoid tissue (MALT) lymphoma infiltraving the leiomyomas of the uterus of a patient. Methods: The routine paraffin slides were cut, stained with HE, immunochemically by ABC methodusing the and stained by Feulgen method. Then the DNA ploidy of tumor cells was measured with an image cytometer. Results: In the mucosa, submucosa and the smooth muscle layer of the stomach and in the leiomyomas of the uterus there was diffusive and dense infiltration of centrocyte-like cells. The DNA measurement results were that the distribution of DNA mass of lymphoma cells in stomach and in lymph nodes had a single main aneuploidy peak each, and the distribution of DNA mass of lymphoma cells in leiomyomas of uterus had two peaks; one of them was the diploid, the other aneuploid. Conclusion: The MALT lymphoma cell invasion in uterus must be differentiated with a primary lymphoma in the uterus, the chronic lymphocyte leukemia in uterus and an endometrial stromal sarcoma. The present prognosis of the patient under discussion was poor. The follow-up results indicated the DNA index seemed to be important for predicting the malignancy degree and prognosis.

THE IMMUNOHISTOCHEMISTRY AND QUANTITATIVE MORPHOMETRIC STUDY OF MUCOSA ASSOCIATED LYMPHOID TISSUE(MALT)LYMPHOMA IN STOMACH

Objective: To invetigate the Immunohistochemistry characters and quantitative nmorphometric significance for the mucosa associated lymphoid tissue (MALT) lymphoma of stomach in 14 patients. Methods: The routine paraffin slides were cut, stained with H.E., and immunochemically by ABC method. The morphologic appearance of nuclei of lymphoma cells were measured with HPIAS-1000 color pathology picture analysis system. Results of the 14 cases, 9 was centrocyte like (CCL) cell lymphoma, 2 CCL with large cell lymphoma, 1 small no cleaved cell lymphoma, 1 large no cleaved cell lymphoma, 1 T immunoblastic malignant lymphoma. The morphologic measurement results showed that there were great significant differences (P<0.001) for the 15 items of morphology parameters between the nuclei of MALT lymphoma cells and those of normal control lymphocytes in stomach. There were great significance differences (P<0.001) or significance (P<0.05) for the most of the 15 items of morphologic parameters of nuclei among the 5 types of MALT lymphoma. Especially, that the values of area, circumference, equivalent diameter, area volume, circumference volume, long diameter, short diameter, practical area were increasing as the malignant degree of classification was rising, which reflect the increasing malignancy of the tumor. Conclusion: It was suggested that with the quantitative morphology measurement method, man could make accurate diagnosis for MALT lymphoma. It offered us a new method to make the diagnosis, so that it had significance. It might be also practicable with morphology measurement method to make the sub classification of MALT lymphoma.

Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Colon in a Patient with <i>Borrelia burgdorferi</i>Infection (Lyme Arthritis)

Mucosa-associated lymphoid tissue (MALT) lymphoma generally occurs in the context of chronic inflammation or autoimmune disorders. The most common infections linked to MALT lymphomas include Helicobacter pylori (Hp)-associated gastritis, Chlamydophila psittacii and hepatitis C infection. Although Borrelia burgdorferi infection has been linked to primary cutaneous B-cell lymphoma (PCBCL), there is no known link between Borrelia burgdorferi infection and MALT lymphomas in the US. We report a patient who developed mucosa-associated lymphoid tissue (MALT) lymphoma of the colon in the context of untreated Lyme arthritis, and no other autoimmune disorders or infections known to be associated with MALT lymphoma. We recommend that Lyme disease due to Borrelia burgdorferi be considered as a possible underlying infection potentially contributing to the emergence of extranodal lymphoma.

幽门螺旋杆菌感染与MALT1基因易位对胃MALT淋巴瘤免疫微环境的影响及意义

目的探究幽门螺旋杆菌(helicobacter pylori,HP)感染和黏膜相关淋巴组织淋巴瘤易位基因1(mucosa-associated lymphoid tissue lymphoma translocation gene 1,MALT1)易位对胃黏膜相关淋巴组织(mucosa-associated lymphoid tissue,MALT)淋巴瘤免疫微环境及患者预后的影响。方法通过免疫组化染色检测40例胃MALT淋巴瘤患者石蜡活检样本中CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、Foxp3^(+)调节性T细胞(Treg)、CD68^(+)巨噬细胞、CD163^(+)M2型巨噬细胞、CD83^(+)树突状细胞(dendritic cell,DC)、CD56^(+)自然杀伤细胞(natural killer cell,NK)和CD33^(+)髓源抑制细胞(myeloid-derived suppressor cells,MDSC)的浸润情况。利用HE染色对患者HP感染情况进行判定,同时采用FISH检测40例胃MALT淋巴瘤中MALT1基因易位情况,根据HP感染和MALT1基因易位情况进行分组,比较免疫微环境及患者预后的差别。结果40例胃MALT淋巴瘤中HP感染阳性率为80%(32/40)。FISH技术鉴定MALT1基因易位阳性率为7.5%(3/40)。9种免疫细胞浸润水平的对比分析中HP阴性组CD4^(+)T细胞浸润水平显著高于HP阳性组(78.73/HPF vs 40.42/HPF,P<0.001),而MALT1易位阳性组CD56^(+)NK浸润水平(2.76/HPF vs 5.58/HPF,P<0.05)显著低于MALT1易位阴性组。HP阴性组患者的无进展生存率显著低于HP阳性组(P<0.05)。结论HP阴性组中CD4^(+)T细胞浸润水平显著高于HP阳性组,且可能与患者预后相关;MALT1易位阳性组中CD56^(+)NK细胞浸润水平显著低于易位阴性组,提示MALT1易位可能影响以NK细胞为代表的部分先天免疫。

一线化疗治疗眼附属器MALT淋巴瘤临床疗效

本研究分析一线化疗治疗眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT)的临床疗效。回顾性分析8例眼附属器MALT淋巴瘤患者的临床资料。给予3例ⅠE期患者COP/CHOP方案治疗。给予5例Ⅳ期患者COP/CHOP联合利妥昔单克隆抗体。结果表明:完全缓解(CR)加部分缓解(PR)的有效率100%,3例ⅠE期患者获得PR,5例Ⅳ期患者获CR,中位随访时间21个月,患者疾病无进展,3例ⅠE期患者仍持续PR,5例Ⅳ期患者持续CR。结论:眼附属器MALT淋巴瘤呈惰性临床过程,化疗安全有效,联合利妥昔单克隆抗体方案能明显提高缓解率,可以作为一线治疗方案。

甲状腺原发MALT淋巴瘤12例临床病理、免疫表型及IgH基因重排研究

目的:观察甲状腺原发MALT淋巴瘤的临床病理表现、免疫组织表型和免疫球蛋白重链(IgH)基因重排情况。方法:对12例甲状腺原发MALT淋巴瘤进行回顾性研究,包括临床病理表现、免疫表型(CD20、CD45RO、CD5、CD10、CyclinD1、bcl-2、κ、λ)分析及多聚酶链反应(PCR)检测IgH基因重排。结果:按2001新版WHO关于淋巴造血组织肿瘤分类,12例均被确诊为MALT淋巴瘤。其中男2例,女10例,男女之比为1:5,中位年龄为63岁。免疫表型检测:所有病例之瘤细胞均表达B细胞分化抗原CD20;4例(33.3%)检测出免疫球蛋白轻链限制性表达;bcl-2阳性1例;CD45RO、CD5、CD10和CyclinD1均为阴性。8/12例(66.7%)检测出IgH基因克隆性重排。随访11例,失访1例,死亡3例(25%),存活8例(66.7%)。结论:甲状腺原发MALT淋巴瘤属惰性淋巴瘤,需要结合其病理组织形态、免疫组织化学染色及必要的分子生物学技术才能作出正确的诊断。

MALT淋巴瘤57例临床病理及克隆性分析

目的通过观察57例MALT淋巴瘤的组织形态学特点,结合免疫组化和分子病理学诊断方法,完善对MALT淋巴瘤的诊断与鉴别诊断。方法根据HE染色和免疫组化(CD20、bcl-2、CD3、CD5、CD10、CD23和cyclin D1)检测,对所有标本进行组织学评价,并应用DNA-PCR和免疫组化(kappa/lambda)检测免疫球蛋白基因重排和轻链的限制性表达。结果 157例MALT淋巴瘤,镜下常呈弥漫性生长,少数表现为结节样。MALT淋巴瘤细胞类型多样,在具有腺上皮的组织,如胃、肠、唾液腺等处常出现淋巴上皮病变(LEL)。LEL的形成是其诊断的重要依据。2肿瘤细胞的克隆性检测:57例MALT淋巴瘤中有35例出现Ig H基因单克隆性重排,占61.4%(35/57)。免疫组化:15例kappa或lambda的表达具有优势,敏感性为26.3%(15/57);其中4例Ig H基因单克隆性重排(-),而kappa或lambda(+)。两者联合应用的阳性率为68.4%。结论尽管MALT淋巴瘤缺乏特异性诊断性抗体,但是通过组织形态学特征以及免疫组化的检测,可以将MALT淋巴瘤与其他B细胞性淋巴瘤鉴别。将检测免疫球蛋白重链基因重排及轻链限制性表达,作为MALT淋巴瘤诊断的辅助检查方法具有明显的应用价值。

原发性胃肠非MALT型淋巴瘤的临床与病理分析

目的：研究胃肠原发性非ＭＡＬＴ型淋巴瘤形态特征、诊断要点和鉴别诊断，为临床治疗和预后提供依据。方法：胃肠淋巴瘤标本常规制片，免疫组化ＡＢＣ法标记，光镜观察。结果：３１例非ＭＡＬＴ型淋巴瘤中：（１）肠病相关／不相关Ｔ细胞淋巴瘤２１例，其中肠病相关１６例；（２）ＭＭＣＬ３例在肠道呈息肉样，套细胞增生或浸润反应性滤泡内。（３）ＭＦＬ２例亦呈息肉样或形成肿块，由中心细胞和中心母细胞组成；（４）大多叶核淋巴瘤２例；（５）组织细胞性３例。结论：ＭＡＬＴ型、ＭＭＣＬ和ＭＦＬＢ细胞性淋巴瘤为３种不同细胞起源，形态相似、免疫表型相同和不相同之处，有助于诊断和鉴别诊断。肠病相关Ｔ细胞淋巴瘤有独特临床病理特征，易误诊为肠道炎性病变而延误诊断和治疗。

T(11;18)及核bcl-10蛋白在胃肠MALT淋巴瘤中的表达

为了探讨t(11;18) (q2 1;q2 1)染色体易位及核bcl 10蛋白在胃肠粘膜相关淋巴组织淋巴瘤 (MALTlym phoma)中的表达 ,用酸性酚氯仿法从石蜡组织中提取RNA ;逆转录合成cDNA后用聚合酶链反应 (PCR)扩增API2 MALT1融合基因 ;用免疫组织化学法检测石蜡切片中bcl 10蛋白的表达。结果表明 :4 2例MALT淋巴瘤中 ,t(11;18)(q2 1;q2 1)染色体易位在低度恶性MALT淋巴瘤中的表达为 14 % ,在伴高恶转化型MALT淋巴瘤中的表达为 4 6 % ,在 4 0例弥漫大B细胞淋巴瘤 (diffuselargeBcelllymphoma ,DLBCL)对照组中没有表达 ;4 3例MALT淋巴瘤中bcl 10蛋白在低度恶性MALT淋巴瘤的核表达为 6 1% ,在伴高恶转化型MALT淋巴瘤中的核表达为 6 9%。结论 :t(11;18)易位可能与高度进展MALT淋巴瘤有一定相关性 ,但与DLBCL无关 ;bcl 10蛋白的核表达在恶性程度不同的两组MALT淋巴瘤中无显著性差异 ,其原因有待进一步研究。

肠MALT淋巴瘤细胞凋亡与p53和bc-l2的表达

目的 探讨肠黏膜相关淋巴组织 (MALT)淋巴瘤细胞增殖和凋亡的特征以及凋亡相关调控基因的表达。方法 应用TUNEL技术检测 2 1例肠淋巴瘤的凋亡指数 (apoptosisindex,AI) ,免疫组化S P法检测PCNA增殖指数(proliferativeindex ,PI)及bcl 2和p5 3蛋白的表达。结果 随着肠MALT淋巴瘤恶性度的增高 ,AI和PI显著增加 ,并且二者呈显著正相关。低度恶性、高度恶性伴低度恶性以及高度恶性肿瘤组中 ,bcl 2阳性率分别为 79 4%、5 7 1%、40 9%。三组bcl 2阳性率及AI均差异显著 (P <0 0 5 )。bcl 2与AI呈显著负相关 (P <0 0 5 )。p5 3阳性率为 31 4%。高度恶性组p5 3阳性率显著高于其余两组。p5 3与bcl 2表达呈负相关 (P <0 0 5 )。结论 凋亡和增殖在肿瘤的发生、发展、转化中起着重要作用 ,检测AI、PI可能是诊断恶性淋巴瘤、评价其生物学行为的可靠指标。在MALT的恶性度从低到高的转化中 ,p5 3和bcl

原发性MALT淋巴瘤API2-MALT1融合基因多种变异体的表达及其意义

检查API2-MALT1融合基因多种变异体mRNA在MALT淋巴瘤中的表达情况,探讨其表达与MALT淋巴瘤的临床病理特征及预后的关系。方法:收集胃和肺MALT淋巴瘤石蜡包埋标本共29例,慢性淋巴结炎5例。采用RT-PCR和巢式PCR相结合检测MALT淋巴瘤中API2-MALT1的mRNA。将29例分为API2-MALT1mRNA表达组及未表达组,了解两组患者临床病理学特征和预后的差异。结果:MALT淋巴瘤中两种API2-MALT1变异体被检出,总检出率为48.2%,慢性淋巴结炎未检出,与未表达组相比,表达组临床病理分期偏低,细胞增殖活性和淋巴结受累有降低和减轻的趋势,两组间病变范围、浸润深度等特征及预后无明显差异。结论:API2-MALT1mRNA的表达可能与MALT淋巴瘤的淋巴结受累、临床病理分期及细胞增殖有关,与MALT淋巴瘤的浸润深度、病变范围及预后等无明显相关;不同的变异体表达与MALT淋巴瘤的发生部位有关。

H.pylori相关胃MALT淋巴瘤患者胃黏膜中β-防御素2及核因子-κB的表达研究

目的:研究人β-防御素2(HBD-2)与核因子-κB(NF-κB)在幽门螺杆菌(H.pylori)相关胃黏膜相关淋巴组织(MALT)淋巴瘤患者胃黏膜中的表达情况,探讨HBD-2与NF-κB在胃MALT淋巴瘤中的作用和相互关系。方法:收集40例在根除治疗前H.pylori(+)且根除治疗后H.pylori为(-)的胃MALT淋巴瘤患者的胃黏膜组织作为病例组,同时收集36例H.pylori(-)的慢性浅表性胃炎患者胃黏膜组织作为对照组,用免疫组化法检测HBD-2与NF-κB的表达情况。结果:HBD-2与NF-κB在H.pylori相关胃MALT淋巴瘤中的表达水平高于对照组(P<0.01);根除H.pylori治疗后,HBD-2与NF-κB表达水平降低(P<0.01);HBD-2与NF-κB呈现正相关。结论:HBD-2与NF-κB参与了H.pylori相关胃MALT淋巴瘤的发病过程。