老年人EB病毒阳性弥漫大B细胞淋巴瘤临床病理学特点及预后分析

目的 探讨老年人EB病毒阳性（EBV＋）弥漫大B细胞淋巴瘤（DLBCL）的临床病理学特点及预后.方法 采用回顾性研究的方法 ,收集24例老年EBV＋DLBCL患者,以同期EBV-非特指型DLBCL患者为对照,分析老年EBV＋ DLBCL患者的临床病理学特点及预后.结果 24例老年EBV＋DLBCL患者肿瘤细胞形态上主要表现为单一性或多形性肿瘤细胞增生;多形性病例中常可见有地图状坏死.细胞起源免疫分型主要为非生发中心亚型,分别占91.3％（Hans分型）和100.0％（Choi分型）.CD30阳性率为55.0％,高于非特指型EBV-DLBCL（P＜ 0.001）.在总体生存时间方面,R-CHOP方案治疗的老年EBV＋DLBCL患者和＞50岁EBV-DLBCL患者的中位生存时间分别为44.2个月和29.2个月,两者差异无统计学意义（P=0.587）.结论 老年人EBV＋DLBCL肿瘤细胞形态上主要表现为单一性或多形性肿瘤性增生;多形性病例中常可见不规则坏死.CD30阳性率较高,并且主要为非生发中心B细胞亚型.R-CHOP方案治疗的老年EBV＋ DLBCL患者的总体生存时间与同年龄段非特指型EBV-DLBCL患者相近.     

EB病毒阳性老年人弥漫大B细胞淋巴瘤研究进展

 在2008版的WHO分类中EB病毒（EBV）阳性老年人弥漫大B细胞淋巴瘤（DLBCL）作为新的类型被单独特别列出。就其发病机制、病理学特征及鉴别诊断、发现DLBCL中的EBV的方法进行讨论,另外还就DLBCL患者中EBV感染状态潜在的预测和预后价值及对这类肿瘤的治疗策略进行讨论。     

bcl-6、p53、c-myc基因异常在弥漫大B细胞淋巴瘤中的临床意义

目的 探讨bcl-6 、p53、c-myc基因异常的检测在弥漫大B细胞淋巴瘤（DLBCL）中的临床意义.方法 间期荧光原位杂交（I-FISH）方法检测59例DLBCL患者活体石蜡组织bcl-6、p53蛋白、c-myc基因异常的情况,同时以CHOP及R-CHOP方案化疗,评价疗效.观察bcl-6、p53蛋白、c-myc基因与化疗疗效及生存期的关系.结果 59例DLBCL中,p53丢失18例（30.5％）,bcl-6重排11例（18.6％）,c-myc重排5例（8.5％）.p53丢失阳性组化疗有效率（33.3％）明显低于阴性组（76.5％）（x2=9.560,P=0.002）. bcl-6基因重排阳性组的预后差于基因重排阴性组,但差异无统计学意义[总生存（OS）,P=0.107;无进展生存时间（PFS）,P=0.094]; p53基因丢失阳性组预后明显差于阴性组（OS,P=0.031;IPFS,P=0.028）;c-myc重排阳性组的预后差于基因重排阴性组,但差异无统计学意义（OS,P=0.163;PFS,P=0.167）.其中CHOP化疗组患者,p53基因丢失、c-myc重排阳性组的预后明显差于阴性组,差异有统计学意义（P值均＜ 0.05）;R-CHOP化疗组,bcl-6基因重排阳性组具有较差的预后意义（OS,P=0.003;PFS,P=0.007）.结论 bcl-6 、p53、c-myc基因异常与 DLBCL预后密切相关,可作为预测DLBCL的预后因素并指导治疗.     

幽门螺杆菌感染在胃弥漫大B细胞淋巴瘤中的临床意义：基于83例患者分析

摘 要：［目的］ 探讨幽门螺杆菌（helicobacter pylori,Hp）感染与胃弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）患者临床病理特征的关系及其对预后的意义。［方法］ 纳入江苏省肿瘤医院2010年5月至2019年12月诊治的83例原发性胃弥漫性大B细胞淋巴瘤患者,根据Hp检测结果分为Hp阳性组(41例)和Hp阴性组(42例),对病变标本进行免疫组化检测。治疗后,分析患者的预后及其影响因素。［结果］ Hp阳性组的完全缓解(complete response,CR)率明显高于Hp阴性组(75.6% vs 38.0%,P=0.001)。全组患者中位随访时间为53个月(4~127个月),5年总生存率（overall survival,OS）、无进展生存率(progression-free survival ,PFS)分别为84.8％、79.0％。Hp阳性组患者的预后明显优于Hp阴性组,5年OS分别为95.1％和75.0％（P=0.019）,5年PFS分别为92.3％和66.3％（P=0.009）。Hp阴性且行巩固放疗的患者比非巩固放疗患者有明显的生存获益,5年OS分别为86.3％和61.2％（P=0.046）。单因素分析显示,ECOG评分（P=0.018）、临床分期（P=0.001）、IPI评分（P<0.001）、治疗前LDH水平（P<0.001）、血红蛋白水平（P=0.014）、白蛋白水平（P=0.002）、Hp感染（P=0.019）是OS和PFS的影响因素。多因素分析显示,临床分期、治疗前血红蛋白水平是PFS的独立影响因素,临床分期、治疗前LDH水平是OS的独立影响因素。Hp阳性组的C-myc蛋白（P=0.037）及Bcl-2蛋白（P=0.003）表达阳性率明显低于Hp阴性组,但Bcl-6蛋白表达在两组间无明显差异（P=0.931）。Bcl-6蛋白阳性的胃弥漫大B细胞淋巴瘤患者5年OS（P=0.024）和5年PFS（P=0.045）比Bcl-6蛋白阴性患者更佳,而C-myc蛋白和Bcl-2蛋白阳性患者的预后更差。［结论］ Hp阳性的胃弥漫大B细胞淋巴瘤对化疗反应更好,预后更佳。临床或许可以通过Hp检测结果指导患者是否采取巩固放疗。同时,应进一步实施临床和分子研究,以完善胃弥漫大B细胞淋巴瘤的预后评估体系。     

结外NK/T细胞淋巴瘤检测EB病毒与疗效关系的研究*

目的:探讨血浆中EB病毒阳性在评价结外NK/T细胞淋巴瘤近期疗效和远期疗效中的临床意义。方法:收集2011年1 月至2014年4 月郑州大学第一附属医院经病理及免疫组化确诊为结外NK/T细胞淋巴瘤的患者109 例,应用qRT-PCR方法检测其血浆中EBV-DNA拷贝数,比较EBV 阴性和EBV 阳性患者对治疗疗效与预后的差异。结果:109 例结外NK/T细胞淋巴瘤患者,53例阳性患者中有34例（64.2%）为晚期（Ⅲ～Ⅳ期）,56例阴性患者中22例（39.3%）为晚期（Ⅲ～Ⅳ期）,EBV 阳性组中伴有B 症状33例（62.3%）,阴性组患者21例（37.5%）,EBV 阴性患者与EBV 阳性患者在分期及B 症状方面均具有统计学意义（P<0.05）。 34例（60.7%）EBV 阴性结外NK/T细胞淋巴瘤患者达到客观缓解率,显著高于EBV 阳性患者的客观缓解率（22例,41.5%）（P<0.05）。EBV 阴性组与EBV 阳性组相比,其2 年无进展生存期更高（P<0.05）。 结论:检测结外NK/T细胞淋巴瘤患者血浆中EB病毒对评价其近期疗效及2 年无进展生存期具有重要的临床意义。      

血管免疫母细胞性T细胞淋巴瘤并发EB病毒阳性弥漫大B细胞淋巴瘤二例并文献复习

目的:探讨血管免疫母细胞性T细胞淋巴瘤（AITL）并发EB病毒（EBV）阳性弥漫大B细胞淋巴瘤（DLBCL）患者的临床病理特征、治疗及预后。方法:回顾性分析解放军总医院第五医学中心2例AITL并发EBV阳性DLBCL患者的临床资料,并进行文献复习。结果:例1为混合淋巴瘤（CL）患者,以低热伴全身浅表淋巴结肿大起病,右侧腋窝肿物活组织检查示AITL并发EBV阳性DLBCL,予以8个周期化疗后达不确定的完全缓解;后续应用西达本胺维持治疗,仍生存中。例2为不一致性淋巴瘤（DL）患者,以皮下结节起病,后出现浅表淋巴结进行性肿大;皮下结节病理检查诊断为DLBCL,右腹股沟淋巴结病理检查诊断为AITL;接受7个周期化疗,因合并噬血细胞综合征而死亡。结论:AITL合并EBV阳性DLBCL罕见,临床症状主要以AITL的表现为主,存在T细胞及B细胞免疫表型特征,预后差,治疗方案主要依据预后较差的淋巴瘤进行选择。     

80例原发中枢神经系统弥漫大B细胞淋巴瘤的临床病理、免疫表型及EB病毒感染的研究

目的:对80例原发中枢神经系统弥漫大B细胞淋巴瘤（primary diffuse large B cell lymphoma of the central nervous system,PCNS DLBCL）进行临床病理学回顾性研究、免疫表型检测及EB病毒（Epstein-Barr virus,EBV）感染检测。旨在探讨其与预后的关系。方法:对80例PCNS DLBCL进行免疫表型检测及EB病毒检测,并进行Hans、Choi和Tally分型、统计学单因素和多因素预后分析。结果:Bcl-2、CD10、Bcl-6、Mum-1、GCET-1、BLIMP-1、FOXP-1和LMO-2的表达率分别为46.1%、8.8%、75.0%、57.5%、27.5%、11.3%、75.0%和26.3%;Ki-67指数为30%～95%,中位数为80%。Hans、Choi和Tally分型中Non-GCB型/ABC型弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）（63.9%、79.2%和90.0%）为最常见的亚型。EBV及EBER1/2-ISH的表达率均为3.8%。58.8%的患者术后未行其它治疗,其1年、2年和5年生存率分别为36.3%、16.4%和4.6%。术后是否行其它治疗、采用甲氨喋呤（methotrexate,MTX）治疗和环磷酰胺+多柔比星+长春新碱+泼尼松龙（cyclophosphamide,doxorubicin,vincristine,and prednisone,CHOP）治疗是有统计学意义的预后相关因素（P均＜0.001）。结论:80例PCNS DLBCL患者年龄较国内外报道的小;以Non-GCB型/ABC型DLBCL为主;个别病例检出EB病毒感染;术后未行其它治疗组、未采用MTX治疗组和未CHOP治疗组的预后较差。     

MYC在弥漫大B细胞淋巴瘤的表达及其临床意义

目的 探讨MYC在弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）中的表达及其与预后的关系。方法 回顾性分析广西医科大学附属肿瘤医院2011年2月至2018年8月收治的220例弥漫大B细胞淋巴瘤患者的临床资料。采用免疫组织化学法检测MYC蛋白在DLBCL组织中的表达,并分析其与患者临床病理特征及预后的关系。检索GEO（gene expression omnibus）数据库中有生存资料和基因表达数据的DLBCL数据集,分析MYC基因表达与预后的关系。结果 220例DLBCL组织中MYC蛋白阳性表达率为18.64%,MYC蛋白表达阳性患者总生存期（overall survival,OS）及无进展生存期（progress-free survival,PFS）较阴性表达患者明显缩短（P＜0.001）。亚组分析显示,在GCB免疫亚型中,MYC蛋白表达阳性患者较阴性患者OS明显缩短（P＜0.001）;在non-GCB免疫亚型中,MYC蛋白表达阳性患者较阴性患者的OS及PFS明显缩短（P＜0.001）。Cox比例风险回归模型分析结果显示,MYC蛋白阳性表达是影响DLBCL患者预后的独立危险因素（P<0.01）。GEO数据库中数据集GSE10846分析结果显示MYC基因高表达患者OS明显著缩短（P＜0.01）。结论 MYC蛋白阳性表达的DLBCL患者预后较差。     

口腔颌面部弥漫大B细胞淋巴瘤69例临床病理分析

目的探讨口腔颌面部弥漫大B细胞淋巴瘤（DLBCL）的临床病理学特点及其预后相关因素。方法对69例口腔颌面部DLBCL进行回顾性临床病理分析,包括形态学复习、免疫表型和EB病毒编码小RNA（EBV—EBER）原位杂交检测,结合临床随访结果进行预后相关因素分析,并与同期诊断的40例原发淋巴结DLBCL进行比较。结果69例口腔颌面部DLBCL患者中位发病年龄61岁（4—91岁）,男女比例为1．56：1。发病部位以舌根最为常见（19例,27．5％）,其次为腮腺、齿龈、腭等。肿瘤细胞多起源于非生发中心B细胞,比例为64．2％（43／67）,bcl-2、c—myc及EBV—EBER阳性率分别为66．7％（38／57）、23．4％（11／47）及5．3％（3／57）,Ki-67高表达（t〉70％）者占71．0％（49／69）。42例获得完整随访资料,生存时间1—85个月,生存分析显示年龄I〉65岁、Ki-67高表达者预后差,R-CHOP方案治疗组预后好于CHOP方案及放疗组。与同期诊断为原发淋巴结DLBCL相比,除了肿瘤细胞的起源分组有明显差异外,其余临床病理特点及预后差异均无统计学意义（均P〉0．05）。结论口腔颌面部DLBCL最常见于舌根,多为非生发中心B细胞起源,临床病理特点及预后与淋巴结DLBCL相似。年龄≥65岁和Ki．67高表达是独立的预后不良提示因素。R—CHOP方案治疗组预后好于CHOP方案治疗组。     

R-CHOP和CHOP方案治疗两种亚型弥漫大B细胞淋巴瘤患者的近期疗效

背景与目的：根据肿瘤细胞起源不同,可将弥漫大B细胞淋巴瘤（diffuselarge Bcelllymphoma,DLBCL）分为生发中心来源（germinalcenter Bcell like,GCB）及非生发中心来源（non-GCB）两种亚型。在以CHOP方案为标准的化疗基础上,前者预后优于后者。本研究通过比较R-CHOP（Rituximab联合CHOP）和CHOP方案治疗不同亚型DLBCL患者的近期疗效,寻找初诊DLBCL患者最佳一线治疗方案。方法：将2006年11月至2008年2月中山大学肿瘤防治中心内科收治的83例初治DLBCL患者分为GCB和non-GCB两组。按照修订版淋巴瘤疗效评价标准,比较接受R-CHOP或CHOP方案治疗患者的近期疗效;观察Bcl-2在两种亚型中的表达情况,并分析其与近期疗效的关系。结果：83例DLBCL患者中GCB组35例（42．2％）,non-GCB组48例（57．8％）。GCB组一线化疗近期总缓解率74．3％,non-GCB组60．4％,两组相比差异有显著性（P=0．006）。Bcl-2在GCB和non-GCB两亚组的表达差异没有显著性：Bcl-2阳性患者采用R．CHOP方案治疗的近期缓解率（75．6％）明显高于用CHOP方案治疗者（47．8％）,两组相比差异有显著性（P=0．031）：采用不同方案化疗的Bcl-2阴性患者的近期缓解率则差异无显著性（P〉0．05）。结论：GCB组患者接受标准R—CHOP或CHOP方案治疗近期缓解率高于non-GCB组,提示预后良好。加用Rituximab可提高Bcl-2阳性患者的近期缓解率。     

Epstein-barr virus-positive gastric carcinoma has a distinct protein expression profile in comparison with epstein-barr virus-negative carcinoma.

PURPOSE: EBV has been detected in 2-16% of gastric carcinomas. However, there is little information available about the gene expression profile of EBV-positive gastric carcinomas. EXPERIMENTAL DESIGN: EBV infection was examined using EBV-encoded small RNAs (EBERs) in situ hybridization, and 63 (5.6%) of 1127 consecutive gastric carcinomas were found to be EBV-positive. The expressions of 27 tumor-associated proteins were evaluated immunohistochemically in 63 EBV-positive gastric carcinomas and 287 EBV-negative carcinomas using the tissue array method. In addition, the genotype of EBV was investigated by PCR amplification of LMP1 (latent membrane protein 1), Epstein-Barr nuclear antigen 2 (EBNA2), and EBNA3B genes. RESULTS: EBV-positive gastric carcinomas are characterized by the presence of lymphoid stroma, proximal location, and predominance in males. In comparison with EBV-negative carcinomas, EBV-positive carcinomas showed frequent loss of expression of p16, smad4, FHIT, and KAI-1 (kangai 1; P < 0.05), but retained the expression of APC (adenomatous polyposis coli), DCC (deleted in colorectal cancer), and some DNA repair proteins (P < 0.05). There was negative association between EBV infection and the expression of MUC1, MUC2, MUC5AC, p53, CEA, C-erbB2, and smad7. Using hierarchical cluster analysis, we divided EBV-positive gastric carcinomas into two clusters. Those patients with cluster 1 (42 cases) carcinomas had a better prognosis than those with cluster 2 (12 cases; P = 0.0002) or those with EBV-negative carcinomas (280 cases; P = 0.0251). Fifty-one (92.7%) of 55 EBV-positive carcinomas demonstrated the 30-bp deletion in LMP1 gene, and 53 (96.4%) of 55 cases were type 1 for EBNA2 and EBNA3B genes. CONCLUSION: EBV-positive gastric carcinomas have a distinct protein expression profile as well as distinct clinicopathological features, as compared with EBV-negative carcinomas. The subclassification of EBV-positive carcinomas, by hierarchical cluster analysis, is significantly associated with patient survival.     

EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement.

PURPOSE: Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity. PATIENTS AND METHODS: Using a validated polymerase chain reaction/enzyme immunoassay-based prescreening method in combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2% (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N = 566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial. RESULTS: EBV-positive gastric carcinomas occurred significantly more frequently in males (P <.0001) and in younger patients (P =.012). Most were of the intestinal type according to the Laurén classification (P =.047) or tubular according to the WHO classification (P =.006) and located in the proximal part of the stomach (P <.0001). A significantly lower tumor-node-metastasis system-stage (P =.026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node (LN) involvement (P =.034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P =.04) and a significant better cancer-related survival (P =.02), was observed for these patients, which could be explained by less LN involvement, less residual disease, and younger patient age. CONCLUSION: EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.     

Autocrine growth of Epstein-Barr virus-positive gastric carcinoma cells mediated by an Epstein-Barr virus-encoded small RNA

Although 5-10% of gastric carcinoma (GC) cases worldwide are associated with EBV, a human herpesvirus, it is still not clear what the precise contribution of the virus is to the pathogenesis of EBV-positive GC. Here we report that EBV infection induces expression of insulin-like growth factor 1 (IGF-I) in the GC-derived EBV-negative cell line NU-GC-3 and that the secreted IGF-I acts as an autocrine growth factor. Transfection of individual EBV latent genes into NU-GC-3 cells revealed that the EBV-encoded small RNA (EBER) was responsible for IGF-I expression. Addition of recombinant IGF-I accelerated growth of NU-GC-3 cells, whereas growth of the EBV-converted NU-GC-3 cells was blocked by treatment with an anti-IGF-I antibody. These results suggest that IGF-I induced by EBER acts as an autocrine growth factor for EBV-positive GC. These findings seem to be operative in vivo, as EBV-positive GC biopsies consistently express IGF-I, whereas EBV-negative GC biopsies do not. EBER is invariably expressed in EBV-associated malignancies including GC. The present findings strongly suggest that EBV directly affects the pathogenesis of EBV-positive GC and underline the importance of RNA molecules on cell growth regulation.     

Infrequent Overexpression of p53 Protein in Epstein-Barr Virus-associated Gastric Carcinomas

Epstein-Barr virus (EBV) infection was studied in a total of 412 patients with poorly differentiated gastric adenocarcinoma by in situ hybridization for EBV-encoded small RNA. EBV-speciflc RNA was detected in tumor cell nuclei of 83 (20.1%) of 412 gastric carcinomas, of which 60 were histologically subclassified as gastric carcinoma with lymphoid stroma (GCLS). All EBV-positive gastric carcinomas as well as 90 randomly selected EBV-negative gastric carcinomas were further studied for p53 protein expression by immunohistocbemistry. The Overexpression of p53 protein was demonstrated in only 7 (8.4%) of 83 EBV-positive gastric carcinomas. This was in marked contrast to the frequency of 34.4% in EBV-negative gastric carcinomas. In addition, a few p53-positive nuclei were characteristically scattered in the tumors of many EBV-positive GCLS, but this was not regarded as p53 Overexpression arising from mutation of the gene. Our findings suggested that EBV-associated gastric carcinomas may arise through a different mechanism from other types of gastric carcinomas without EBV infection.     

CD30在EBV阳性弥漫性大B细胞淋巴瘤中的表达及其预后意义北大核心

目的:探讨CD30在EBV阳性弥漫性大B细胞淋巴瘤(EBV-positive diffuse large B-cell lymphoma,EBV+DLBCL)中的表达及预后意义。方法:回顾性分析322例DLBCL中EBV+DLBCL与EBV-DLBCL病例临床病理参数之间的关系,以及CD30在EBV+DLBCL中的表达及预后意义。结果:CD30在EBV+DLBCL病例中的表达多于EBV-DLBCL病例(P=0.002);EBV-DLBCL中双表达的病例多于EBV+DLBCL(P=0.044);在63例EBV+DLBCL中,CD30阳性表达多见于B症状患者(P=0.015);另外有2例EBV+DLBCL病例出现BCL6基因重排。随访139例患者中,共表达CD30和EBER的患者预后较差(P=0.002);在EBV+DLBCL中,CD30阳性提示预后更差(P=0.028)。结论:CD30在EBV+DLBCL病例中具有较高的表达率,且与患者不良预后相关,进一步为靶向药物的使用提供理论依据。     

五种异质性弥漫大B细胞淋巴瘤微环境细胞PD-1表达及意义

目的弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)是一组具有明显异质性的大细胞淋巴瘤,通过多种检查手段早期识别DLBCL预后较差的亚群,对于预后判断和治疗选择具有重要作用。本研究选择了几种相对少见免疫表型表达的DLBCL类型(C-myc/Bcl-2共表达、NF-κB/p65阳性、CD5阳性及CD30阳性的DLBCL)和EB病毒(epstein-barr virus,EBV)阳性的DLBCL病例进行研究,通过检测肿瘤微环境细胞中程序性死亡受体-1(programmed death receptor-1,PD-1)表达情况,探讨PD-1表达相关的影响因素及其表达对相应DLBCL发生和发展的影响。方法收集贵州医科大学附属医院2010-01-01-2018-08-31诊断的120例DLBCL患者资料,通过普通免疫组化染色(C-myc、Bcl-2、NF-κB/p65和CD30)、免疫组化双标(CD5、PAX5)及EBER原位杂交检测筛选出上述特殊类型的病例并分组,普通免疫组化染色检测肿瘤微环境中PD-1蛋白表达情况。收集临床病理资料并随访,对实验数据进行统计学分析。结果120例DLBCL患者中,PD-1肿瘤浸润淋巴细胞(tumor infiltraling lymphoeytes,TILs)阳性病例共有63例(52.5%,63/120);其中C-myc/Bcl-2共表达组中PD-1(+)-TILs病例27例(69.25%,27/39),NF-κB/p65阳性组30例(68.2%,30/44),CD30阳性组17例(73.9%,17/23),CD5阳性组14例(77.8%,14/18),EBV阳性组中为5例(55.6%,5/9)。PD-1(+)-TILs与PD-1(-)-TILs组病例之间IPI评分(χ^2=4.514,P=0.034)和Ann Arbor分期(χ^2=4.760,P=0.029)差异有统计学意义,PD-1(+)-TILs组分期晚、IPI指数高;PD-1-TILs表达在阳性组C-myc/Bcl-2共表达(χ^2=6.485,P=0.011)、NF-κB/p65(χ^2=6.851,P=0.009)、CD30(χ^2=5.232,P=0.022)、CD5(χ^2=5.426,P=0.040)表达率明显高于阴性组,差异有统计学意义;PD-1-TILs表达在EBV阳性组与阴性组之间差异无统计学意义,χ^2=0.001,P=0.970。生存分析98例随访病例中,PD-1(+)-TILs组病例的总生存率(overall survival,OS)明显低于PD-1(-)-TILs组患者,χ^2=14.652,P<0.001;在C-myc/Bcl-2共表达(χ^2=4.071,P=0.049)、NF-κB/p65的核表达(χ^2=4.833,P=0.025)及CD30阳性DLBCL(χ^2=5.207,P=0.024)中PD-1(+)-TILs组的生存状况也明显较PD-1(-)-TILs组病例差;多因素回归分析显示,PD-1(+)-TILs是DLBCL的独立危险因素,HR=38.170,P=0.036。结论PD-1表达在C-myc/Bcl-2共表达阳性、NF-κB/p65阳性、CD30阳性和CD5阳性的DLBCL中明显增高,在EBV阳性的DLBCL中增加不明显,PD-1在肿瘤微环境细胞中的表达可能是(C-myc/Bcl-2共表达阳性、NF-κB/p65阳性和CD30阳性)DLBCL不良预后评估的相关因素。