Molecular Subtypes,Apoptosis and Proliferation Status in Indonesian Diffuse Large B-Cell Lymphoma Cases

Objective: The diffuse large B-cell lymphoma (DLBCL) has two major molecular subtypes, germinal center B-cell-like (GCB) and non-GCB. These have differing behavior which affects overall patient survival. However, immunohistochemistry based molecular subtyping of Indonesian DLBCLs has been limited. This was the focus of the present study, with a focus of attention on the apoptotic index (AI) and the proliferation index (PI) of the two molecular subtypes. Materials and Methods: During the study period of 3.5 years, a total of 98 cases of DLBCL were identified. Molecular subtypes and PI were determined by immunohistochemistry and TUNEL method was used to determine the AI. Result: GCB accounted for 31 cases (31.6%) and non-GCB the remainder (68.4%). Gender showed a slight male predominance (54 cases, 55.1%), with a higher incidence in the extra-nodal region (57 cases, 58.2%). The AI and PI were significantly higher in GCB (pConclusion: The findings indicate that the non-GCB subtype is more common than GCB in Indonesian DLBCL. GCB features significantly higher PI and AI, which themselves appear linked.     

Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma:a report of 76 cases

Pediatric diffuse large B-cell lymphoma （DLBCL） is a highly aggressive disease with unique clinical characteristics. This study analyzed the germinal-center type B-cell （GCB） classification and clinical characteristics of Chinese pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat- sen University Cancer Center between February 2000 and May 2011, with an age younger than 18 years, were included in the analysis. The male/female ratio was 3.47：1. The median age was 12 years （range, 2 to 18 years）, and 47 （61.8%） patients were at least 10 years old. Of the 76 patients, 48 （63.2%） had stage Ill/IV disease, 9 （11.8%） had bone marrow involvement, 1 （1.3%） had central nervous system （CNS） involvement, and 5 （6.6%） had bone involvement. The GCB classification was assessed in 45 patients： 26 （57.8%） were classified as GCB subtype, and 19 （42.2%） were classified as non-GCB subtype. The modified B-NHL-BFM-90/95 regimen was administered to 50 patients, and the 4-year event-free survival （EFS） rate was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification： 17 （54.8%） were classified as GCB subtype, with a 4-year EFS rate of 88.2%; 14 （45.2%） were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our data indicate that bone marrow involvement and stage III/ IV disease are common in Chinese pediatric DLBCL patients, whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype. The modified B-NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.     

219例弥漫性大B细胞淋巴瘤免疫表型及遗传学特征分析

  目的  探讨国内弥漫性大B细胞淋巴瘤（DLBCL）免疫表型分型及BCL-2和BCL-6基因异常的分布情况。  方法  应用组织芯片和免疫组织化学法及FISH技术对219例DLBCL的免疫表型及BCL-2和BCL-6基因异常进行检测,根据Hans法进行分型;并收集国内7家相关研究报道,进行综合分析。  结果  本组研究结果:219例DLBCL中,非GCB型（165例,75.3%）显著高于GCB型（54例,24.7%）（P < 0.001）。BCL-2基因异常共49例（25.8%）,其中t （14;18）5例（2.6%）均为GCB型;BCL-2基因扩增44例（23.2%）,GCB型4例（8.5%）,非GCB型40例（28.0%）,有显著性差异（P=0.013）。BCL-6基因重排共42例（22.1%）,GCB型7例（14.9%）,非GCB型35例（24.5%）,差异无统计学意义（P=0.189）。BCL-2基因扩增和BCL-6基因重排呈显著负相关（r=-0.180,P=0.013）。8组综合分析:1 259例中非GCB型（879例,69.8%）明显高于GCB型（380例,30.2%）（P < 0.001）;免疫表型中CD10和MUM1阳性率组间差异较小（P=0.047和P=0.048）,而BCL-6及BCL-2阳性率组间存在明显差异（P < 0.001）。  结论  我国DLBCL患者在主要免疫表型和遗传学特征方面具有独特性,对此值得进行深入研究。      

乳腺弥漫大B细胞淋巴瘤临床特点及预后分析

目的:探讨乳腺弥漫大B细胞淋巴瘤（DLBCL）患者的临床特征及预后。方法:回顾性分析2014年5月起至2018年12月我院收治的18例乳腺DLBCL患者的临床特点及预后。结果:在18例患者中,17例为女性,中位年龄为57岁,病变主要累及右侧乳腺（11/18,61.1%）。将其分为原发性乳腺DLBCL（PB-DLBCL）和继发性乳腺DLBCL（SB-DLBCL）两大类。11例（57.6%）PB-DLBCL与7例（42.4%）SB-DLBCL相比,其具有Ann Arbor分期多为Ⅰ-Ⅱ期（P＜0.01）、B症状少（P=0.013）、相对更高的白细胞计数（P=0.041）、骨髓未累及（P=0.043）、完全缓解（CR）率高（P=0.049）等特点。生存分析发现PB-DLBCL患者5年总生存期（OS）显著长于SB-DLBCL患者（P=0.013）。本研究以非生发中心B细胞型（non-GCB）居多,生发中心型（GCB）与non-GCB型之间OS无显著差异（P=0.885）。所有获得CR患者的生存期均显著延长（P=0.008）。结论:乳腺DLBCL多见于中年女性,以右侧乳腺肿块为主要临床表现,分子分型多为non-GCB型。与SB-DLBCL患者相比,PB-DLBCL患者具有Ann Arbor分期早、B症状少、相对更高的白细胞计数、骨髓未累及、CR率高等特点,并且生存期显著延长。无论是PB-DLBCL和SB-DLBCL,还是GCB型和non-GCB型,获得CR提示预后良好。     

弥漫大B细胞性淋巴瘤分子亚型的蛋白表达研究

目的：在蛋白水平上研究国人弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）分子分型的蛋白表型特点,为DLBCL的病理诊断、预后和治疗提供依据。方法：取DLBCL标本52例行HE染色和免疫组化染色。在形态学分型的基础上,利用CD10、MUM1和bcl-6免疫标记对DLBCL进行分子分型,分为生发中心样B细胞样组（germi-nal center B-cell-like,GCB）和非生发中心样B细胞样组（non-germinal center B-cell-like,non-GCB）,分析其在DLBCL中的构成比,及CD10、MUM1和bcl-6的表达情况。结果：本组DLBCL中,non-GCB的构成比超过GCB（69.2%/30.8%）;统计学分析表明,GCB组间CD10、bcl-6、CD10/bcl-6的表达率的差异有显著性意义,其中CD10的表达率最高,bcl-6其次,CD10/bcl-6最低;non-GCB组间MUM1、MUM1/bcl-6的表达率的差异有显著性意义。结论：我国的DLBCL多起源于后生发中心B细胞,以non-GCB为主,预后较差。DLBCL在CD10、MUM1和bcl-6表达的差异对判定GCB组和non-GCB组有意义。     

Prognostic Values of Various Clinical Factors and GeneticSubtypes for Diffuse Large B-cell lymphoma Patients: ARetrospective Analysis of 227 Cases

Aim: To analyze the significance of different clinical factors for prognostic prediction in diffuse large B-celllymphoma (DLBCL) patients. Methods: Two hundred and twenty-seven DLBCL patients were retrospectivelyreviewed. Patients were managed with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)regimen or rituximab plus the CHOP (RCHOP) regimen. Results: Lactate dehydrogenase (LDH), β2-microglobulin (β2-M), B symptoms, Ann Arbor stage and genetic subtypes were statistically relevant in predictingthe prognosis of the overall survival (OS). In the CHOP group, the OS in patients with germinal center B-celllike(GCB)(76.2%) was significantly higher than that of the non-GCB group (51.9%, P=0.032). With RCHOPmanagement, there was no statistical difference in OS between the GCB (88.4%) and non-GCB groups (81.9%,P=0.288). Conclusion: Elevated LDH and β2-M levels, positive B symptoms, Ann Arbor stage III/IV, and primarynodal lymphoma indicate an unfavorable prognosis of DLBCL patients. Patients with GCB-like DLBCL have abetter prognosis than those with non-GCB when treated with the CHOP regimen. The RCHOP treatment withthe addition of rituximab can improve the prognosis of patients with DLBCL.     

Correlation Between Immunophenotype Classification and Clinicopathological Features in Chinese Patients with Primary Gastric Diffuse Large B-Cell Lymphoma

Recent studies have shown that diffuse large B-cell lymphoma (DLBCL) can be classified into germinal center B-cell–like (GCB) and non-GCB phenotypes by immunohistochemical staining. The aim of this study was to investigate the correlation of immunophenotypic classification with clinicopathological features in Chinese patients with primary gastric DLBCL to further our knowledge of this disease. Seventy-three patients with a histopathological diagnosis of primary gastric DLBCL were studied. Immunohistochemistry was carried out using the EnVision method to detect the expression of CD10, Bcl-6, and MUM1. The clinicopathologic features and follow-up data were analyzed using the Kaplan–Meier method, log-rank test, and χ ² test. Expression of CD10 was observed in 21.9 % (16/73) of patients, Bcl-6 in 72.6 % (53/73), and MUM1 in 74.0 % (54/73). According to these data, 32.9 % (24/73) of the cases belonged to GCB subtype and 67.1 % (49/73) belonged to non-GCB subtype. There was a significant difference in tumor size and local lymph node metastasis between the GCB and non-GCB groups (P?<?0.05). Complications in the GCB group (4.2 %) occurred less frequently than those in the non-GCB group (18.4 %); however, this difference was not significant (P?>?0.05). Survival analysis revealed that patients in the GCB group had an increased 5-year survival rate compared to those in the non-GCB group (58.5 % vs 35.7 %, χ ²?=?3.939, P?<?0.05). The 5-year survival rate of patients undergoing R-CHOP chemotherapy was significantly longer than that of patients in the CHOP group (74.7 % vs 37.5 %, χ ²?=?4.185, P?<?0.05). The immunophenotype classification of primary gastric DLBCL, which is closely related to the tumor size and local lymph nodes metastasis, was found to have prognostic significance.     

Serum neuron-specific enolase is correlated with clinical outcome of patients with non-germinal center B cell-like subtype of diffuse large B-cell lymphoma treated with rituximab-based immunochemotherapy

The present study examines the clinical significance of serum neuron-specific enolase (NSE) in patients with non-germinal center B-cell type (non-GCB) of diffuse large B-cell lymphoma (DLBCL) that received rituximab chemotherapy. Serum NSE values were measured using electrochemiluminescence assay in 53 patients. About 54.7% of the DLBCL patients had positive expression of serum NSE (>15.20 ng/ml), which closely correlated with performance status, serum LDH level, B symptoms, IPI scores, and Ann-Arbor stages (P < 0.05). The mean serum NSE value in patients with non-GCB subtype of DLBCL was significantly higher than that of GCB subtype of DLBCL (P = 0.001), and among patients in non-GCB subtype group, there was significant difference in the 5-year OS rate between NSE-positive group and negative group (28.3% vs. 81.6%, P < 0.001). Furthermore, serum NSE level was found to be an independent prognostic factor in patients with non-GCB subtype. Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic factor for non-GCB subtype of DLBCL in the era of rituximab.     

Cell of origin fails to predict survival in patients with diffuse large B-cell lymphoma treated with autologous hematopoietic stem cell transplantation

Diffuse large B-cell lymphoma (DLBCL) includes two prognostically important subtypes, the germinal center B-cell (GCB) and the non-GCB types. The aim of this study was to evaluate immunohistochemical approaches for predicting the survival of patients with DLBCL following autologous hematopoietic stem cell transplantation (AHSCT). We identified 62 patients with DLBCL who either had an initial complete remission (17 patients) or received salvage chemotherapy for relapsed or refractory disease (45 patients), followed by AHSCT. Tissue microarrays were immunostained with monoclonal antibodies against GCET1, CD10, BCL6, MUM1, FOXP1 and LMO2. Using the Hans algorithm, we classified 50% of the cases as GCB type, whereas the Choi algorithm classified 58% as GCB type and LMO2 was positive in 69%. However, no significant differences were found in the 5-year overall or event-free survivals using any of these approaches. In conclusion, cell of origin fails to predict survival of DLBCL patients treated with AHSCT.     

miR-320d与弥漫大B细胞淋巴瘤预后的相关性研究

目的 探讨miR-320d表达与弥漫大B细胞淋巴瘤（DLBCL）预后的关系.方法 应用EnVision法对山西省肿瘤医院有随访资料的原发于淋巴结的DLBCL 62例石蜡标本进行CD20、CD3、CD10、bcl-6、Mum-1免疫标记检测,根据Hans分类方法将DLBCL分为生发中心B细胞（GCB）型和非生发中心B细胞（non-GCB）型.采用安捷伦16.0高密度芯片对24例DLBCL石蜡标本进行miRNA表达谱筛选,用实时荧光定量PCR方法对62例DLBCL石蜡标本进行miR-320d表达验证.将1 1例淋巴结反应性增生标本作为对照.结果 62例DLBCL中,GCB型22例（35.5％）,non-GCB型40例（64.5％）,GCB型miR-320d表达水平是non-GCB型的3.43倍（P=0.034）.miR-320d在对照组的表达量是DLBCL的5.65倍（P＜ 0.001）.单因素分析示DLBCL中miR-320d低表达组总生存期低于高表达组,差异有统计学意义（P=0.021）.多因素Cox回归模型分析示62例DLBCL中,miR-320d低表达（RR=2.434,95％CI1.148～5.159,P=0.020）为独立于国际预后指数（IPI）的预后不良因素.结论 miR-320d表达下调预示DLBCL预后不良.     

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-celllymphoma (DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen (R-CHOP regimen)significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001),Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and-negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.     

Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas.

PURPOSE: The reliability of immunohistochemistry for subdividing diffuse large B-cell lymphomas (DLBCL) into germinal center B-cell-like (GCB) and non-GCB prognostic subgroups is debated. In this study we evaluated the prognostic significance of such subgrouping on a series of 153 DLBCL patients. Furthermore, we investigated whether both subgroups could comprise clinicopathologic entities recognized by their morphology and characterized by a distinct phenotype, specific genetic abnormalities, and clinical characteristics. PATIENTS AND METHODS: All samples from patients were reviewed and morphologically subdivided into large cleaved, immunoblastic, and not otherwise specified DLBCL. GCB and non-GCB immunohistochemical profiles were established. The presence of chromosomal translocations involving BCL2, BCL6, and MYC and/or rearrangements of these genes was investigated. RESULTS: Subdividing DLBCL with either a GCB or non-GCB immunophenotypic profile was not of prognostic significance. Nevertheless, CD10 expression was a predictor of favorable outcome, whereas high bcl-2 expression and BCL6 rearrangement were adverse predictors of disease-free survival. Interestingly, large cleaved DLBCL was clearly associated with a GCB immunophenotypic profile, CD10 expression, BCL2 rearrangement, age younger than 60 years, and low to low/intermediate International Prognostic Index risk, but was not of prognostic significance. In contrast, immunoblastic morphology was associated with a non-GCB profile and was a significant predictor of unfavorable DFS. CONCLUSION: Subdividing DLBCL into subgroups based on their immunohistochemical profile was not of prognostic significance. Nevertheless, it allowed the additional characterization of two lymphoma subgroups previously recognized in the Working Formulation. Both correspond to two distinct clinicopathologic entities within the DLBCL.     

Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era

We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 ( P  = 0.022) or Bcl-6 ( P  = 0.021), or GCB subtype ( P  = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 ( P  = 0.001) or MUM1 ( P  = 0.011), or non-GCB subtype ( P  = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group ( P  = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group ( P  < 0.001) and also in the R-CHOP group ( P  < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated. ( Cancer Sci  2009; 100: 1842–1847)     

弥漫大B细胞淋巴瘤免疫亚型与临床特征及疗效的关系

目的探讨弥漫大B细胞淋巴瘤(DLBCL)免疫亚型与一线CHOP化疗方案的疗效关系。方法采用免疫组化链霉素抗生物素蛋白-过氧化物酶连接法(SP)检测60例DLBCL石蜡组织中MUM-1、bcl-6和CD10的表达,确定弥漫大B细胞淋巴瘤免疫亚型。60例患者均采用CHOP或CHOP样方案化疗,观察各组的疗效及不良反应。结果弥漫大B细胞淋巴瘤GCB型和非GCB型各30例,GCB型组患者完全缓解率、稳定率合有效率分别为56.7%、6.7%和93.3%,非GCB型租患者完全缓解率、稳定率及有效率分别为26.7%、13.3%和76.7%,两组患者疗效差异有统计学意义(P<0.05)。GCB型组患者3年生存率明显高于非GCB型组,差异有统计学意义(P<0.05)。两组患者不良反应差异无统计学意义(P>0.05)。结论 DLBCL免疫学亚型与CHOP方案疗效存在一定关系,可以作为预后判断的重要因素。     

弥漫大B细胞淋巴瘤两种预后亚型患者的外周血T细胞亚群动态监测

 　目地　检测弥漫大B细胞淋巴瘤（DLBCL）患者两种预后亚型（生发中心型和非生发中心型）不同治疗阶段的T细胞亚群分布,评估患者的T细胞免疫功能状态。方法　采用流式细胞术（FCM）检测34例DLBCL患者发病初、化疗期间、疗程结束后外周血中的CD+3、CD+4、CD+8和CD+4 CD+25 T细胞的分布情况。以16名健康人外周血作为对照。结果　DLBCL两种预后亚型患者化疗前外周血中CD+4 T细胞比例和CD4／CD8比值分别为（32.27±2.00）%和（0.81±0.39）,明显低于正常水平;CD+8 T细胞、CD+4 CD+25 T细胞比例分别为（40.80±6.23）%和（5.68±5.45）%,明显增高。而CD+3 T细胞比例则在整个治疗过程中保持稳定状态,与正常水平比较差异均无统计学意义（均P＞0.05）。化疗3个周期后CD+8 T细胞逐渐减少,而CD+4、CD+4 CD+25 T细胞、CD4／CD8比值则明显上升,至化疗6个周期结束后除了CD+4 CD+25 T细胞仍明显高于正常及化疗前水平外,余各项指标与正常水平比较差异均无统计学意义（均P＞0.05）。至化疗结束3个月后,CD+4 CD+25 T细胞逐渐下降至接近正常,除了化疗前生发中心型CD+3 和CD+8 T细胞比例[分别为（74.83±3.59）%和（40.80±6.23）%]高于非生发中心型[分别为（68.26±3.56）%和（33.76±5.46）%],不同治疗时期DLBCL患者两种预后亚型间各项指标差异均无统计学意义（t值分别为2.039、2.419,P值分别为0.041、0.018）。不同时期DLBCL患者两种预后亚型间各指标差异均无统计学意义（均P＞0.05）。结论　不同基因亚型DLBCL患者不同治疗时期均存在不同程度的细胞免疫受抑,动态监测T细胞亚群的变化可以实时了解患者的T细胞免疫功能状况。     

Evaluating Cell-of-Origin Subtype Methods for Predicting Diffuse Large B-Cell Lymphoma Survival: A Meta-Analysis of Gene Expression Profiling and Immunohistochemistry Algorithms

BackgroundPatients with DLBCL exhibit widely divergent outcomes despite harboring histologically identical tumors. Currently, GEP and IHC algorithms assign patients to 1 of 2 main subtypes: germinal center B cell-like (GCB), or activated B cell-like (ABC), the latter of which historically carries a less favorable prognosis. However, it remains controversial as to whether these prognostic groupings remain valid in the era of rituximab therapy.Materials and MethodsA systematic literature review identified 24 articles from which meta-analyses were conducted, comparing survival outcomes for patients assigned to either GCB or ABC/non-GCB subtype using GEP and/or Hans, Choi, or Muris IHC algorithms.ResultsPatients designated as GCB DLBCL using GEP fared significantly better in terms of overall survival than those with ABC DLBCL (hazard ratio, 1.85; P < .0001). In contrast, the Hans and Choi algorithms failed to identify significant differences in overall survival (P = .07 and P = .76, respectively) between GCB and non-GCB groups.ConclusionsOur study illustrates a lack of evidence supporting the use of the Hans and Choi algorithms for stratifying patients into distinct prognostic groups. Rather, GEP remains the preferred method for predicting the course of a patient's disease and informing decisions regarding treatment options.     

Prognostic relevance of immunohistochemical subclassification of diffuse large B-cell lymphoma in two prospective phase III clinical trials

Purpose:Until now molecular biologic techniques have not been easily used in daily clinical practice to stratify patients for therapeutic purposes. Therefore, we have investigated the prognostic relevance of the immunohistochemical (IHC) germinal center B-cell (GCB) versus non-GCB diffuse large B-cell lymphoma (DLBCL) subtypes.Patients and Methods:We have analyzed tumor samples from patients treated in 2 prospective multicenter phase III trials, ie HOVON 25 (patients ≥ 65 years, n = 153) and HOVON 26 (patients < 65 years, n = 144) using whole sections (WS) or tissue microarray (TMA). CD10, BCL6, and MUM1 were applied in a specific IHC algorithm. The effect on clinical outcome using WS or TMA and variations in cut-off levels of these markers was also investigated.Results:The GCB subtype was not associated with a better OS in either trial. Small differences were observed in the HOVON 25 trial between techniques, with TMA showing a better outcome for GCB than did WS. Variation of cut-off levels in the specific algorithm did not improve the prediction of clinical outcome.Conclusion:We did not observe a consistent predictive power of the GCB and non-GCB classification by IHC in this large series of DLBCL patients treated with CHOP. This underscores the need to determine the biologic variation and the standardization of the protein expression levels and to further study the relevance of prognostic IHC classifications, preferably in phase III clinical trials.     

p53 、Ki-67 在弥漫性大B 细胞淋巴瘤中的表达及相互关系

 目的 探讨p53和Ki-67在DLBCL免疫类型中的表达及相互关系。方法 采用免疫组化MaxVision法检测p53和Ki-67在DLBCL免疫类型中和反应性增生的淋巴结中的表达。结果 25例GCB中p53的阳性率为16．0％，35例non-GCB中p53的阳性率为45．7％，两者之间P〈0．01；25例GCB中Ki-67高表达4例，35例non-GCB中Ki-67高表达18例，两者之间P〈O．01；p53阳性DL-BCL20例中ki-67高表达12例，p53阴性DLBCL40例中Ki-67高表达10例，两者正相关。结论 p53、Ki-67的表达与DLBCL的免疫类型相关，GCB类型中低表达，non-GCB类型中高表达。     

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。     

弥漫大B细胞性淋巴瘤中t(14;18)易位及BCL2表达的意义

  目的  探讨弥漫大B细胞性淋巴瘤(DLBCL)中t(14;18)易位及BCL2表达的意义。  方法  用石蜡包埋组织免疫组织化学法检测142例淋巴结、胃肠道和咽淋巴环等不同器官或部位发生的DLBCL中CD10、BCL6、MUM1和BCL2的抗原表达, 按免疫表型将DLBCL分成GCB-DLBCL和非GCB-DLBCL两个亚型; 聚合酶链反应(PCR)扩增75例淋巴结结内DLBCL新鲜组织中由t(14;18)易位所形成的MBR/JH和lnfr/JH重组基因。  结果  142例DLBCL中, 75例(52.8%)表达BCL2。分型为GCB-DLBCL的51例中, 18例(35.3%)表达BCL2;分型为非GCB-DLBCL的91例中, 57例(62.6%)表达BCL2, 两者阳性率比较有显著性差异(P=0.002)。同时, BCL2的表达阳性率按不同器官或部位发生的DLBCL作比较, 结果也存在显著性差异(P=0.01)。18.7%的淋巴结结内DLBCL中有t(14;18)易位, 阳性病例主要见于GCB-DLBCL之中。  结论  t(14;18)易位是GCB—DLBCL亚型的遗传学特征, BCL2表达在不同亚型和不同器官或部位发生的DLBCL中有显著性差异。