EBV潜伏基因产物在恶性淋巴瘤组织中的表达及意义

目的：探讨EBV潜伏基因产物在恶性淋巴瘤组织中的表达及意义。方法：用免疫组化方法对565例NHL、64例HL人体标本进行LMP－1、EBNA2对比检测并选择101例NHL进行PCR检测。结果：EBV－PCR检出率（19．8％）高于LMP－1（14．9％）,PCR阴性病例LMP－1全部为阴性,EBNA2在全部病例均为阴性,在NHL,LMP－1阳性细胞主要是免疫母细胞样细胞、R－S样细胞和R－S细胞,LMP－1阳性的R－S样细胞我数表达活化分子CD30。肠道原发恶性淋巴瘤EBV检出率较高（23．1％）。T淋巴瘤EBV检出率（23．8％）高于B淋瘤（10．2％）。结论：EBV潜伏基因产物表达情况能够反映出宿主细胞的分化程度和（或）宿主的免疫监视作用。EVB在R－S样细胞形成可能起作用。EBV感染与肠道恶性淋巴瘤的发病有关。     

肠道淋巴瘤与EB病毒相关性研究

目的：探讨EB病毒（Epstein-Barr virus,EBV)感染在肠道淋巴瘤发病中的意义。方法：采用EBV的DNA原位杂交及S－P法免疫组化技术（第一抗体为EBV、CD3、CD20、CD43、CD45、CD45RO、CD74等），观察24例肠道淋巴瘤患者（8例肠病相关T细胞淋巴瘤、16例黏膜相关淋巴组织B细胞淋巴瘤）EBV感染情况。以20例慢性结肠炎作为对照。结果：患者年龄21－92岁（平均52．8岁），男女之比为3．8：1。临床上均以腹痛、腹胀或便血就诊。组织病理学：T细胞淋巴瘤细胞多形性、核大，不规则，嗜血管性及大片坏死；B细胞淋巴瘤细胞中等大小，多呈圆形、椭圆形、胞质较少淡染，核稍大，核分裂象多见，可见“淋巴上皮病变”。24例淋巴瘤中检出（原位杂交及免疫组化）EBV－DNA 14例（检出率为58．3％），其中T细胞淋巴瘤EBV的检出率为75％，B细胞淋巴瘤EBV的检出率为50％（P＜0．01）。结论：肠道淋巴瘤的发生与EBV的感染有明显的相关性。     

广西口腔颌面颈部原发性淋巴瘤 EBV感染及其临床病理特征分析

目的：探讨广西地区EBV感染与恶性淋巴瘤病理类型及发病的相关性。方法采用原位杂交技术检测81例口腔颌面颈部淋巴瘤的肿瘤组织中EBV编码的RNA(EBER),并分析其临床病理特征。结果(1)EBER总阳性率为44．4%,霍奇金淋巴瘤占检出率的40%,非霍奇金淋巴瘤占检出率的45．1%,不同细胞来源的非霍奇金淋巴瘤依次占检出率的75%( T细胞淋巴瘤)、87．5%( NK/T细胞淋巴瘤)、2．9%( B细胞淋巴瘤),T细胞、NK/T细胞非霍奇金淋巴瘤EBER阳性率比B细胞非霍奇金淋巴瘤高,差异有统计学意义(P<0．05)。(2)淋巴结内、外淋巴瘤EBER阳性率分别为17．9%、58．5%,二者比较差异有显著性(P<0．05)。(3)50岁以上淋巴瘤患者EBER检出率(36．2%)低于50岁以下患者检出率(55．9%),差异无显著性(P>0．05)。结论广西地区口腔颌面颈部淋巴瘤与EBV感染相关,其中以发生在淋巴结外弥散淋巴组织的NK/T细胞淋巴瘤最为显著。     

肠道非霍奇金淋巴瘤与EB病毒、p53、p21ras的相关性

目的：研究肠道非霍奇金淋巴瘤（NHL）与EB病毒（EBV）感染p53、p21^ras蛋白表达及其相关性。方法：以SABC免疫组化方法检测瘤细胞p53、p21^ras基因的表达及EBV寡核苷酸探针（EBER）原位杂交。结果：19例肠道NHL好发部位小于肠下段和结肠，以单发瘤结节多见，常伴有表面溃疡形成。经免疫组化证实3例为T细胞淋巴瘤（15.79%），16例为B细胞淋巴瘤（84.21%）。依WHO分类，T细胞淋巴瘤为外周T细胞性（2／19例）和T／NK细胞性（1／19例）。EBV－EBER原位杂交3／19例有阳性表达，均为T细胞淋巴瘤，阳性细胞占肿瘤细胞的30％－80％。B细胞淋巴瘤未见阳性。p53的表达共有12例，占全部病例的63.16%，11例有p21^ras的表达，为57.9%，有8例同时检出p53和p21^ras的表达。结论；肠道淋巴瘤以B细胞淋巴瘤多发，并以惰性为多见，如为T细胞性淋巴瘤，提示多是侵袭性，且T细胞淋巴瘤与EBV相关性较高，而B细胞淋巴瘤无相关性。p53的表达与EBV感染无明显相关性，而p21^ras的表达与EBV感染似有关系。     

根据WHO淋巴造血系统肿瘤新分类对山西省淋巴瘤分布特点的分析

目的根据WHO淋巴造血系统肿瘤新分类标准、分析山西省恶性淋巴瘤的分布特点。方法重新阅读HE切片,选用免疫组织化学ABC法标记间变性淋巴瘤激酶（ALK）1、bcl-6、CD（1α、3、4、5、7、8、10,15、20、23、30、43、56、68、79α和99）、细胞周期蛋白（cyclin）D1、上皮膜抗原（EMA）、IgD,k,λ、潜伏膜抗原（LMP）1、PAX5、末端脱氧核苷酸转移酶（TdT）和Vs38C;原位杂交方法标记EBER RNA。按照WHO淋巴造血系统肿瘤新分类标准,对山西省肿瘤医院存档的447例淋巴瘤组织标本重新分类。结果447例淋巴瘤中,385例（86．1％）为非霍奇金淋巴瘤（NHL）,62例（13．9％）为霍奇金淋巴瘤（HL）。68．3％NHL为B细胞来源,30．6％为T和NK细胞来源,组织细胞来源的肿瘤仅占3例（0．8％）。弥漫大B细胞淋巴瘤（DLBCL）为最常见的类型（35．1％）,其他依次为外周T细胞淋巴瘤、非特殊型（PTun,12．0％）、黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤,11．7％）,滤泡性淋巴瘤（FL,8．6％）,前体淋巴母细胞性淋巴瘤（T-LBL,7．0％）,间变性大细胞淋巴瘤（ALCL,4．2％）,小淋巴细胞性淋巴瘤（B-SLL,3．6％）和套细胞淋巴瘤（MCL,2．6％）。263例B细胞淋巴瘤105例（39．9％）表达免疫球蛋白轻链,包括52例K和53例λ。263例B细胞淋巴瘤14例表达LMP-1,14例表达EBER;119例T和NK细胞淋巴瘤6例表达LMP-1,19例表达EBER,NHL中LMP-1和EBER表达具有不一致性。62例HL37例（59．7％）一致表达LMP-1和EBER RNA,包括7例富于淋巴细胞型HL、11例混合细胞型HL和19例结节硬化型HL。结论所搜集到的山西省DLBCL的比率类似于美国、澳大利亚、日本和韩国,FL的比率明显低于美国和澳大利亚。     

非特指性外周T细胞淋巴瘤中EBER、 LMP1的表达及与预后的关系

目的 探讨非特指性外周T细胞淋巴瘤(peripheral T-cell lymphoma,not otherwise specified,PTCL-NOS)中EBER、LMP1的表达及与患者预后的关系.方法 采用原位分子杂交(in situ hybridization,ISH)技术和免疫组化法分别检测81例PTCL-NOS及59例对照组[48例血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T-cell lymphoma,AITL)和11例结外NK/T细胞淋巴瘤(extranodal NK/T cell lymphoma,ENK/TCL)]中EBER和LMP1的表达,并分析EBER表达与PTCL-NOS患者临床病理特征及预后的关系.结果 (1)81例PTCL-NOS中,EBER阳性率为43.2％ (35/81);35例EBER阳性的PTCL-NOS病例中免疫组化得分1分+2分者共29例,占EBER阳性病例的82.9％(29/35),3分+4分者共6例,占17.1％ (6/35).EBER表达与PTCL-NOS患者年龄、性别、乳酸脱氢酶(lactate dehydrogenase,LDH)水平及临床分期均无明显相关性(P＞0.05).(2)81例PTCL-NOS组织中,LMP1蛋白阳性率为22.2％(18/81).LMP1蛋白表达与EBER表达具有一致性,但EBER阳性率明显高于LMP1 (P ＜0.05).(3)33例PTCL-NOS获得临床随访资料,随访时间1～63个月,中位生存期为23个月,总生存率为33.3％(11/33).Kaplan-Meier生存曲线分析显示,EBER阳性组的生存率明显低于EBER阴性组(P＜0.05).结论 EB病毒(EBV)感染可能是PTCL-NOS发生、发展中重要但非根本性的因素.EBER-ISH检测EBV感染具有较高的敏感性和特异性.EBV感染对PTCL-NOS患者的预后判断具有重要意义.     

小B细胞恶性淋巴瘤形态学和免疫组织化学研究

目的：探讨各种小B细胞恶性淋巴瘤的形态学、免疫表型特征及其鉴别诊断。方法：对15例小淋巴细胞性淋巴瘤（SLL）、3例淋巴浆细胞性淋巴瘤（LPL）、36例滤泡性淋巴瘤（FL）、25例套细胞淋巴瘤（MCL）、7例淋巴结边缘区B细胞淋巴瘤（MZL）和30例黏膜相关淋巴细胞型结外边缘区B细胞淋巴瘤（MALT－MZL）的石蜡切片进行HE形态学观察和CD5、CD10、CD23和cyclinD1等抗体的免疫组织化学分析。结果：各种小B细胞恶性淋巴瘤在组成细胞和组织结构上各具特征；免疫表型：SLL表达CD5（82％）和CD23（80％），FL表达CD10（87％），MCL表达cyclinD1（84％）和CD5（80％），MZL／MALT－MZL和LPL均不表达CD5、CD10、CD23和cyclinD1。结论：各种小B细胞恶性淋巴瘤均是独立疾病，各具形态学和免疫表型特征，结合HE形态学观察和CD5、CD10、CD23、cyclinD1等免疫组化分析有助于正确诊断和鉴别诊断。     

原发性中枢神经系统淋巴瘤的临床病理、免疫表型及其与EB病毒相关性研究

目的：观察原发性中枢神经系统淋巴瘤（PCNSL）的临床病理、免疫表型及其与EB病毒的关系。方法：搜集25例PCNSL的临床资料并随访,应用单克隆抗体UCHL－1、L26、k、λ胶质纤维酸性蛋白（GFAP）和CS1－4行免疫组织化学染色,EB病毒寡核苷酸探针（EBER1／2）原位杂交,研究其免疫表型和EB病毒感染情况。结果：25例PCNSL均为B细胞淋巴瘤,EBER1／2原位杂交25例中仅2例（8％）出现阳性。结论：本组PCNSL均为B细胞激性。且与EB病毒呈低相关性。     

淋巴瘤样肉芽肿型大B细胞淋巴瘤

目的 探讨淋巴瘤样肉芽肿型大B细胞淋巴瘤(原名淋巴瘤样肉芽肿病，lymphomatoid granulomatosis，LYG)的病理形态特征、病变性质及鉴别诊断要点。方法 对l例LYG的组织形态学、免疫组织化学、EBV原位分子杂交(EBER)结合临床特征进行了分析。结果 l例63岁男性患者，临床上表现为多系统多器官性病变，主要累及肺，表现为双肺内境界清楚的圆形结节，呈孤立性或弥漫性分布，并出现多发性皮下结节，发热、体重减轻、全身无力等症状。皮下结节活检示多个肉芽肿样结构，细胞形态多样，见组织样细胞、非典型淋巴样细胞、小淋巴细胞、浆细胞及散在多核巨细胞，可见一血管壁有淋巴样细胞浸润，未见明显中心粒细胞，可见核分裂象。肺部穿刺组织示弥漫淋巴样细胞浸润，并见灶性坏死，免疫表型示瘤细胞呈CD20 ，CD79α ，CD43 ,CD3-,GraB-，EBV散在 ，CK-，Syn-，原位杂交示EBER 。结论 本例LYG是一种罕见的淋巴瘤样肉芽肿型大B细胞性淋巴瘤，与EBV相关。临床与影像学上与Wegener肉芽肿相似。肺部出现结节状病灶时，临床上易与结核、肉芽肿病、肺癌及炎性假瘤等相混淆，病理上须与结核、非特异性肉芽肿病、结外的外周T细胞淋巴瘤等相鉴别，形态学、免疫表型结合临床特征可明确诊断。     

不同亚型T细胞淋巴瘤与EB病毒的关系

目的 :探讨不同组织学类型T细胞淋巴瘤 (TCL)与EBV感染的关系。方法 :对 83例 (6种类型 )TCL进行研究 ,包括低度恶性 30例 (其中小多形 2 1例、小淋巴细胞性 9例 ) ,高度恶性 5 3例 (其中大 /中多形 31例、淋巴母细胞性 9例、间变性大细胞性 7例、透明细胞性 6例 )。采用PCR检测EBV特征性的DNA序列 (EBV DNA)和ISH法检测EBV编码的RNA(EBER 1/2 )。结果 :每种类型TCL均有EBV的阳性表达 ,低度恶性组与高度恶性组之间EBER 1/ 2表达率差别有显著性 (P <0 0 5 )。结论 :各种类型TCL的发生发展均与EBV感染有关 ,但高度恶性组EBER 1/ 2的表达比低度恶性组更显著。     

Epstein–Barr virus-associated primary gastrointestinal lymphoma in non-immunocompromised patients in Korea

We examined 81 cases of primary gastrointestinal lymphomas in Korea, including 64 gastric lymphomas and 17 intestinal lymphomas, for EBV expression by EBER-1 in situ hybridization (ISH) and EBNA-1 PCR. In EBER-1 positive cases, we performed immunohistochemistry for latent membrane protein-1 (LMP-1) and EBV diffuse early antigen (EA(D)) to compare EBV latent gene expression and lytic process.   EBER-1 was detected in 15 of 81 cases of lymphomas. EBER-1 expression showed three different patterns on tumour cells; diffuse 4/81 (5%), localized 4/81 (5%), and a few scattered pattern 7/81 (9%). We regarded diffuse pattern and localized pattern as EBER-1 positive group (8/81: 10%). Diffuse pattern of EBER-1 was shown in all three T-cell lymphomas and one B-cell lymphoma. A localized pattern was seen all in B-cell lymphomas. The EBER-1 expression was 11% in the stomach (7/64) and 6% in the intestine (1/17). Five of the eight EBER-1 positive gastric lymphomas were histologically diffuse large B-cell lymphomas, and the other three were peripheral T-cell lymphoma, unspecified, one angiocentric lymphoma, and one intestinal T-cell lymphoma by REAL classification. Eight MALT type gastric B-cell lymphomas showed no EBV association. EBV nuclear antigen (EBNA-1) was detected in 15 of 45 resected cases (33%) by PCR. EBER-1 positive cases were all EBNA-1 positive. Twelve EBNA-positive/EBER-negative cases consisted of seven cases showing a few scattered EBER-1 positive lymphocytes. LMP-1 and diffuse early antigen (EA(D)) was detected in five and three cases, respectively. Although follow-up information in our series was incomplete, it seemed that there was no significant difference in their staging or prognosis between EBER-positive cases and EBER-negative group. It is concluded that EBV is associated with some lymphomas among Koreans without overt pre-existing immunodeficiency, especially in T-cell lymphomas.     

A survey of Epstein-Barr virus gene expression in sporadic non-Hodgkin''s lymphomas. Detection of Epstein-Barr virus in a subset of peripheral T-cell lymphomas.

This study analyzes the association of Epstein-Barr virus (EBV) with non-Hodgkin's lymphoma (NHL) arising in patients without pre-existing overt immunodeficiency. The authors examined 201 lymphomas (105 high-grade B-cell, 82 peripheral T-cell, 7 high-grade non-B-cell, non-T-cell, and 7 hairy-cell leukemia) for EBV gene expression by immunohistologic procedures using monoclonal antibodies to EBV latent, immediate early, and replicative infection antigens. Transformation-associated EBV latent membrane protein 1 (LMP 1) was detected in 13 (6%) NHL, comprising 4 (4%) high-grade B-cell, 8 (10%) peripheral T-cell, and 1 non-B-cell, non-T-cell lymphomas. Anaplastic large-cell lymphoma of T-cell type was consistently LMP 1-negative. EBV nuclear antigen 2 was demonstrated in only three (1%) cases. Induction of replication as defined by expression of the immediate early BamHI Z leftward reading frame 1 (BZLF1) protein was detected in five cases, but early (EA) and late (VCA and MA) lytic cycle antigens were only found in two cases and in one case, respectively. The presence of EBV was confirmed by in situ DNA hybridization in 9 of 11 EBV antigen-positive lymphomas. This study shows the surprisingly frequent presence of EBV in peripheral T-cell NHL in European patients without pre-existing overt immunodeficiency. Interestingly, most sporadic B-cell NHL are not associated with the virus. Furthermore, the usefulness of selected monoclonal antibodies for the routine immunohistological diagnosis of EBV infection was confirmed.     

High frequency of Epstein–Barr virus in Chinese peripheral T-cell lymphoma

Forty-two cases of Chinese T-cell lymphoma were studied for expression of Epstein–Barr virus (EBV) encoded RNA (EBER-1) and EBV latent membrane protein-1 (LMP-1) using in situ hybridization and immunohistochemistry, respectively. EBV was detected in tumour cells in 24/39 peripheral T-cell lymphomas (62%), comprising 18/27 pleomorphic, medium and large cell lymphomas (67%), 4/6 angioimmunoblastic lymphadenopathy-like lymphomas (67%), 2/2 Lennert's lymphomas, 0/2 anaplastic large cell lymphomas, and 0/2 T-zone lymphomas. EBV was not found in three T-lymphoblastic lymphomas. EBV was associated with 12/24 nodal (50%) compared with 12/15 extranodal (80%) peripheral T-cell lymphomas. In EBV positive nodal lymphomas, 9/12 cases (75%) contained less than 10% EBER positive tumour cells. In EBV positive extranodal lymphomas, 9/11 cases (82%) showed EBV gene expression in more than 50% of the tumour cells, and in five of these almost all tumour cells were positive. Lymphomas of the nasopharynx (mainly midline granuloma-type) showed EBER-1 expression in nearly all tumour cells. LMP-1 was detected in 19/23 EBER positive peripheral T-cell lymphomas (83%). Our results show that EBV is strongly associated with peripheral T-cell lymphomas in Chinese. An important role for the virus is suggested in lymphomas of the nasopharynx. The significance of EBV in T-cell lymphomas that contain only a minor population of virally infected tumour cells is currently unclear.     

Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angloimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified

Various patterns of Epstein-Barr virus (EBV)-associated B-cell lymphoproliferation occur in patients with immunodeficiency. We studied 17 cases of T-cell lymphoma displaying extensive EBV-driven B-cell lymphoproliferation or simultaneous/subsequent EBV-associated B-cell lymphoma. In 10 cases of angioimmunoblastic T-cell lymphoma, an uncommonly prominent population of EBV+ atypical, activated, focally confluent large transformed B cells was found in the background of T-cell lymphoma. In 4 cases, an EBV-associated B-cell neoplasm (3 diffuse large B-cell lymphomas, 1 plasmacytoma) occurred in patients with T-cell lymphoma. Three cases were composite lymphomas of a peripheral T-cell lymphoma, unspecified, combined with EBV-associated diffuse large B-cell lymphoma. The transformed B-cell population displayed EBV latency types 2 and 3. Monoclonal and oligoclonal B-cell populations were detected in 5 and 6 cases, respectively. Similar to other states of immunodeficiency, disease-related and therapy-induced immunosuppression in T-cell lymphoma may lead to a prominent EBV-associated B-cell lymphoproliferation and to EBV+ B-cell neoplasms.     

Lymphomas of the oral cavity: histology, immunologic type, and incidence of Epstein-Barr virus infection

The purpose of this study was to determine the histologic class and immunologic phenotype of lymphomas presenting initially in the oral cavity and whether this correlated to a high incidence of Epstein-Barr virus (EBV) infection as has been reported with lymphomas in the nasal cavity. Seventy-one cases of oral lymphomas from the oral pathology referral service were analyzed retrospectively. They were classified according to the Revised European American Lymphoma (REAL) classification system using routine immunohistochemistry. EBV infection was determined by detection of early viral RNA sequences (EBER) and latent membrane protein (LMP-1) expression. Only non-Hodgkin's lymphomas were observed, with a female predominance of 2:1. They were primarily of B-cell origin and histologically classified mainly as large B-cell type (68%); T-cell lymphomas were rare (8%). EBV infection was observed in 14% of the B-cell lymphomas, an incidence rate higher than that reported in studies of B-cell lymphomas not located in the oral cavity but not as high as that observed in pleomorphic T-cell lymphomas (all sites, 36%) or nasal cavity T-cell lymphomas (nearly 100%). Interestingly, EBV proliferation did not correlate with expression of either Bcl-2 or p53.     

Histological characteristics of 21 Papua New Guinean children with high-grade B-cell lymphoma, which is frequently associated with EBV infection

The aim of the present study was to confirm the histopathological features of aggressive B-cell lymphoma in Papua New Guinea (PNG)-an EBV endemic region. The immunophenotypic features and expression of EBV-encoded proteins and RNA in B-cell lymphomas were analyzed in 21 PNG children, and compared to the corresponding features of 17 Japanese children with Burkitt lymphoma (BL). Histological diagnosis of the lymphomas from the PNG children was BL in nine patients; atypical Burkitt/Burkitt-like variant of BL (BLL) in three; diffuse large B-cell lymphoma (DLBCL) in four; and B-lymphoblastic lymphoma (B-LBL) in five. The lymphomas from the PNG children had a high positive rate on EBV-RNA in situ hybridization (EBV-ISH; 66.7%). With regard to the histological typing, 10 of 12 patients (83%) with BL/BLL, one of four (25%) with DLBCL, and three of five (60%) with B-LBL were positive for EBV-ISH. The findings of EBV-positive B-LBL were surprising because it is commonly considered that lymphoblastic lymphoma is not associated with EBV. EBV positivity was not detected in the 12 Japanese patients who were available for the EBV-ISH evaluation. It is concluded that it is possible that a proportion of DLBCL and B-LBL besides BL/BLL are associated with EBV in endemic region.     

Malignant lymphoma of the thyroid. A 30-year clinicopathologic experience and an evaluation of the presence of Epstein-Barr virus.

Lymphoma of thyroid is uncommon, and Epstein-Barr virus (EBV) is found in many lymphomas. We studied the clinicopathologic characteristics in Hong Kong Chinese and analyzed the presence of EBV in thyroid lymphomas by reviewing data collected during 3 decades. We studied EBV gene expression by in situ hybridization and immunohistochemistry. Primary thyroid lymphomas were found in 23 patients (diffuse large B-cell lymphoma, 18; marginal zone B-cell lymphoma, 4; plasmacytoma, 1), and secondary lymphomas were found in 9 patients (diffuse large B-cell lymphoma, 3; Burkitt lymphomas, 2; Burkitt-like lymphoma, 1; hairy cell leukemia, 1; nasal T-cell and natural killer cell lymphoma, 1; and intestinal T-cell lymphoma, 1). Primary thyroid lymphomas were large (mean, 7 cm), found commonly in older women, and often misdiagnosed as undifferentiated carcinomas. Fine-needle aspiration was not helpful for diagnosis. Fifteen patients had Hashimoto thyroiditis. A history of thyrotoxicosis was found in 3 patients, and coexistence of 3 diseases (papillary microcarcinomas, primary thyroid lymphoma, and Hashimoto thyroiditis) was found 4 patients. The 5-year survival rate for primary thyroid lymphoma was 53%. Combined surgery and radiotherapy seemed to be the best treatment. Secondary thyroid lymphomas often were asymptomatic. EBV messenger RNAs were detected in 1 primary and 1 secondary thyroid lymphoma. The EBV gene expression in primary thyroid lymphoma showed a type II latency pattern. Thyroid lymphomas in Chinese had important clinicopathologic features. EBV may have a role in a subset of cases.     

Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma

AIMS: Recurrence of non-Hodgkin's lymphoma with or without transformation is often associated with increased clinical drug resistance and poor prognosis indicating molecular progression. The study addresses the currently poorly understood molecular mechanisms underlying relapsing non-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53 alterations as 5/6 (83%) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non-Hodgkin's lymphoma, as 2/5 (40%) diffuse large B-cell lymphomas and 3/9 (33%) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80%) transformed diffuse large B-cell lymphomas developed MDM2 over-expression. CONCLUSION: Our data are consistent with the notion that p53 alterations are important for the histological transformation of follicle centre lymphoma. However, the data also suggest that relapsing follicle centre lymphomas without overt transformation often have p53 alterations and increased risk of transformation, and that relapse of de novo diffuse large B-cell lymphomas and T-cell non-Hodgkin's lymphomas is associated with p53 alterations. Furthermore, our results are consistent with an association of MDM2 over-expression with histological transformation of both follicle centre lymphoma and marginal zone B-cell lymphoma.     

上呼吸道淋巴瘤的病理,免疫表型及其与EB病毒相关性的研究

目的研究中国北方人上呼吸道淋巴瘤的临床病理学、免疫表型及与ＥＢ病毒的关系。方法应用单克隆抗体ＵＣＨＬ１、Ｌ２６、４ＫＢ５及ＣＳ１４进行免疫组化染色,ＥＢ病毒寡核苷酸探针（ＥＢＥＲ１／２）原位杂交,观察１１２例上呼吸道淋巴瘤的免疫表型及ＥＢ病毒感染情况。结果１１２例上呼吸道淋巴瘤病例中７７例为Ｔ细胞淋巴瘤（６８８％）。３５例为Ｂ细胞淋巴瘤（３１．３％）。ＥＢＶＥＢＥＲ１／２原位杂交１０１例中５４例阳性,各例中阳性细胞占肿瘤细胞的１５０％～８５０％,阳性病例中Ｔ细胞淋巴瘤４８例（８８９％）,Ｂ细胞淋巴瘤６例（１１１％）。结论中国北方人上呼吸道淋巴瘤以Ｔ细胞淋巴瘤为多见,且与ＥＢ病毒有较高的相关性。