【作者】 陈金良；

【导师】 王邦茂； 姜葵；

【作者基本信息】 天津医科大学 ， 内科学， 2008， 硕士

【摘要】 目的总结32例胃黏膜相关淋巴组织淋巴瘤患者的临床、内镜和病理表现特征,探讨胃黏膜相关淋巴组织淋巴瘤的治疗策略。研究第10号染色体同源性磷酸酶-张力蛋白基因表达产物、磷脂酰肌醇3激酶、丝氨酸/苏氨酸蛋白激酶等蛋白在胃黏膜相关淋巴组织淋巴瘤中的表达、意义及相关性。方法回顾性分析经病理证实的32例胃黏膜相关淋巴组织淋巴瘤患者临床相关资料。采用免疫组织化学法对其病理切片中PTEN、PI3K、Akt蛋白的表达进行检测。结果1.32例患者的平均发病年龄为63.0岁,男女比例为1:1.13。常见症状为上腹痛、腹胀、反酸、呕吐等,也有以消化道出血入院者。2.内镜下病变主要分布在胃窦部,约占40.63%;形态多样,以隆起型和溃疡型表现为主。诊断较为困难,首次胃镜检查约25.00%获正确诊断。3.胃MALT淋巴瘤全部起源于B淋巴细胞,CD45RO、CD20、EMA、LCA等为常用的病理诊断标志物。根据Ann Arbor分期,正期4例,ⅡE9例,Ⅲ期14例,Ⅳ期5例。4.本组病例幽门螺杆菌感染率约为88.00%,15例(46.88%)进行了幽门螺杆菌根除治疗。本组病例中,20例(62.50%)接受了手术治疗,手术切除辅以化疗13例,单纯化疗2例。3例获得组织学完全缓解。5.PTEN蛋白在胃黏膜相关淋巴组织淋巴瘤中的阳性率为31.25%,PI3K和pAkt两蛋白在胃黏膜相关淋巴组织淋巴瘤中的阳性率则分别为75.00%和71.88%。6.胃MALT淋巴瘤中PTEN和PI3K阳性表达率呈负相关,相关系数r_s=-0.896,P＜0.001;PTEN和pAkt阳性表达率呈负相关,相关系数r_s=-0.840,P＜0.001;PI3K和pAkt阳性表达率呈正相关,相关系数r_s=0.975,P＜0.001。结论1.胃黏膜相关淋巴组织淋巴瘤的临床表现、内镜下特征和病理特点的认识有待进一步提高。该病临床表现无特异性,对长期上腹痛及有消化道出血表现者应考虑到本病可能。2.病变好发于胃窦,胃镜检查中多处、多次活检有助于早期病例的发现。3.对于诊断困难者,可选用B、T细胞标志物进行免疫组织化学检测。4.幽门螺杆菌在胃黏膜相关淋巴组织淋巴瘤的发病中起着重要作用,对早期阶段患者幽门螺杆菌治疗当属首选。过去,治疗该病以手术为主;目前,根除幽门螺杆菌显示出较好疗效。适宜方案的选择应结合幽门螺杆菌感染情况、病情分期等多种因素而定。5.胃黏膜相关淋巴组织淋巴瘤发生过程中存在着抑癌基因PTEN编码蛋白表达下调,PI3K和Akt蛋白的表达上调,而且PTEN表达的下调和后两者之间存在着负相关。6.本实验结果提示PTEN基因在胃黏膜相关淋巴组织淋巴瘤的发病中起着重要作用,PI3K/Akt通路的异常激活参与了胃黏膜相关淋巴组织淋巴瘤的发生、发展过程,为该病晚期阶段的治疗提供了潜在的靶点。更多还原

【Abstract】 Objective To summarize the clinical,endoscopic and pathologic characteristics of 32 patients with gastric mucosa-associated lymphoid tissue(MALT)lymphoma.To investigate the treatment strategies of the gastric MALT lymphoma.To study the expression and significance of phosphatase and tension homology deleted on chromosome ten(PTEN),phosphatidylinositol-3-kinase(PI3K),serine/threonine protein kinase B(Akt)in gastric MALT lymphoma and analyze their relationship.Methods Clinical and other related materials of 32 patients with gastric MALT lymphoma diagnosed pathologically were retrospectively analyzed.Their pathologic sections were detected for PTEN,PI3K and Akt proteins by immunohistochemical staining.Results1.32 patients with gastric MALT lymphoma had a median age of 63.0 years.The male to female ratio was about 1:1.13.The common symptoms were upper abdominal pain,abdominal distension,acid regurgitation,vomiting and so on. Some of them were admitted for gastrointestinal hemorrhage.2.Under endoscopy,about 40.63%lesions were observed in gastric antrum,which was the most common site.The appearances of gastric MALT lymphoma were manifold,and the main pathological changes were upheaval type and ulcer type. The lymphoma was made definite so difficult that 25.00%cases could be diagnosed by endoscopy correctly at the first time.3.All the gastric MALT lymphoma stemmed from B lymphocyte.Markers such as CD45RO,CD20,EMA,LCA and so on were detected for pathologic diagnosis frequently.According to Ann Arbor staging system,4 cases belonged to stageⅠE, 9 cases belonged to stageⅡE,14 cases and 5 cases were at stageⅢand stageⅣrespectively.4.Helicobacter pylori infection was detected in 22 cases(88.00%),15 cases (46.88%)received H.pylori eradication therapy.Among 32 cases,20(62.50%) accepted surgery,surgery combined with chemotherapy were exerted on 13 patients,2 cases were treated with chemotherapy solely.3 patients achieved histological complete remission.5.The expression rate of PTEN in gastric MALT lymphoma was 31.25%,while the expression rate of PI3K and pAkt was 75.00%and 71.88%respectively.6.In gastric MALT lymphoma,the expression of PTEN was negatively correlated with that of PI3K(r_s=-0.896,P＜0.001).The expression of PTEN was also negatively correlated with that of pAkt(r_s=-0.840,P＜0.001).The expression of PI3K was positively correlated with that of pAkt(r_s=0.975,P＜0.001).Conclusions1.We should attach importance to the clinical,endoscopic and pathologic features of gastric MALT lymphoma.The clinical manifestations showed nonspecific. Patients who suffered from upper abdominal pain and gastrointestinal hemorrhage might be diagnosed as gastric lymphoma.2.Gastric MALT lymphoma was often detected at gastric antrum.Endoscopy could help find out the early focus,multiple biopsies could raise the rate of diagnosis.3.As for those hard to be diagnosed definitely,B and T cellular markers could be detected by immunohistochemical assay.4.H.pylori played an important role in pathogenesis of gastric MALT lymphoma. H.pylori eradication should be the first choice to treat gastric MALT lymphoma at early stage.In the past,surgery was the major strategy in treating gastric MALT lymphoma.However,H.pylori eradication has shown a good curative effect nowadays.As for the adaptive schemes,H.pylori infection,pathologic conditions and many other factors should be concerned.5.In gastric MALT lymphoma,expression of the encoding products of anti-oncogene PTEN was down-regulation,while the expressions of PI3K and pAkt were up-regulation.Moreover,the expression of PTEN was negatively correlated with that of PI3K and pAkt.6.These data suggest that PTEN may play an important role in pathogenesis of gastric MALT lymphoma.The abnormal activation of gastric MALT lymphoma correlated with its occurrence and development and it provided a potential therapeutic target.更多还原