Translocations involving the immunoglobulin heavy chain gene locus predict better survival in gastric diffuse large B-cell lymphoma.

PURPOSE: The pathogenesis and clinical heterogeneity of gastric diffuse large B-cell lymphoma (DLBCL) are poorly understood. We have comprehensively investigated the incidence and clinical significance of lymphoma-associated chromosomal translocations, particularly those involving the immunoglobulin heavy chain (IGH) gene locus, in a large series of gastric DLBCL. EXPERIMENTAL DESIGN: One hundred forty-one cases of primary gastric DLBCL [58 with mucosa-associated lymphoid tissue (MALT) lymphoma and 83 without MALT lymphoma] were enrolled. Translocations involving BCL6, c-MYC, FOXP1, MALT1, and IGH were investigated using interphase fluorescence in situ hybridization. In positive cases, additional fluorescence in situ hybridization was done with appropriate probes for potential partner genes. Cases were classified into germinal center B-cell-like (GCB) or non-GCB subgroups by immunophenotyping with CD10, BCL6, and MUM1. RESULTS: Translocations involving IGH were detected in 36 (32%) of 111 cases; their partner genes included BCL6 (n = 10), c-MYC (n = 5), and FOXP1 (n = 3) but remained unknown in the remaining 18 cases. t(14;18)/IGH-BCL2, t(14;18)/IGH-MALT1, and t(1;14)/BCL10-IGH were not detected in any case. t(11;18)/API2-MALT1 was detected in none of the cases, except for one case of DLBCL with MALT lymphoma, which showed positive signals only in MALT lymphoma cells. IGH-involved translocation was associated with younger age but not with any other clinicopathologic factors including GCB or non-GCB immunophenotypes. Cox multivariate analysis revealed that IGH-involved translocation, in addition to younger age and early stage, was an independent prognostic factor for better overall and EFSs. CONCLUSION: IGH-involved translocations are frequent in gastric DLBCL and seem to identify cases with favorable prognosis.     

Immunoblastic morphology in diffuse large B-cell lymphoma is associated with a nongerminal center immunophenotypic profile

Diffuse large B cell lymphomas (DLCBL) are a group of lymphomas whose biologic and prognostic diversity has been recently well characterized. There is also morphologic heterogeneity, but the relevance of subclassification remains uncertain. The World Health Organization Classification states that pathologists have the choice to use only the term diffuse large B-cell lymphoma or to use one of the specific morphologic variants. The aim of the present study was to evaluate if there is an association between immunoblastic morphology and the immunophenotypic profile in DLBCL. Two observers reviewed 117 DLBCL cases. Cases of immunoblastic lymphoma and cases of centroblastic polymorphic lymphoma with more than 50% immunoblasts were defined as having immunoblastic morphology. Immunohistochemistry was performed on tissue microarray slides to establish the immunophenotypic profile. Patients with immunoblastic morphology more frequently had a non-GCB phenotype (94% vs 6%). This finding suggests that the morphological subclassification of DLBCL does have biological meaning, in line with recent evidence indicating that the immunoblastic morphology should not be overlooked in lymphoma classification.     

Array‐comparative genomic hybridization profiling of immunohistochemical subgroups of diffuse large B‐cell lymphoma shows distinct genomic alterations

Diffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic and molecular levels. Subtypes include germinal center B-cell-like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL, according to microarray analysis, and germinal center type or non-germinal center type by immunohistochemistry. Although some reports have described genomic aberrations based upon microarray classification system, genomic aberrations based upon immunohistochemical classifications have rarely been reported. The present study aimed to ascertain the relationship between genomic aberrations and subtypes identified by immunohistochemistry, and to study the pathogenetic character of Chinese DLBCL. We conducted immunohistochemistry using antibodies against CD10, BCL6 and MUM1 in 59 samples of DLBCL from Chinese patients, and then performed microarray-based comparative genomic hybridization for each case. Characteristic genomic differences were found between GCB and non-GCB DLBCL from the array data. The GCB type was characterized by more gains at 7q (7q22.1, P < 0.05) and losses at 16q (P ≤ 0.05), while the non-GCB type was characterized by gains at 11q24.3 and 3q13.2 (P < 0.05). We found completely different mutations in BCL6+ and BCL6− non-GCB type DLBCL, whereby the BCL6− group had a higher number of gains at 1q and a loss at 14q32.13 (P ≤ 0.005), while the BCL6+ group showed a higher number of gains at 14q23.1 (P = 0.15) and losses at 6q (P = 0.07). The BCL6− group had a higher frequency of genomic imbalances compared to the BCL6+ group. In conclusion, the BCL6+ and BCL6− non-GCB type of DLBCL appear to have different mechanisms of pathogenesis.     

Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin.

PURPOSE: Whether diffuse large B-cell lymphoma (DLBCL) of primary central nervous system origin (PCNSL) is biologically different from DLBCL of peripheral nodal origin (NL) remains unclear. The purpose of this study was to compare the expression frequencies and prognostic significance of a panel of cell differentiation markers between these two disease entities. EXPERIMENTAL DESIGN: This study included HIV-unrelated patients with PCNSL (n = 51) and NL (n = 72) treated at four hospitals in Taiwan for whom archival tumor tissue was available. Immunohistochemistry for CD10, BCL-6, MUM-1, vs38c, CD138, and BCL-2 was done. CD10, BCL-6, and MUM-1 expression results were used to classify all cases into the germinal center B-cell (GCB) or the non-GCB subgroup. The prognostic significances of clinical and immunophenotypic markers were evaluated. RESULTS: Nuclear MUM-1 expression was significantly higher in PCNSL than in NL (P < 0.001; 84% versus 53%). PCNSL tumors were more frequently classified into the non-GCB subgroup than NL tumors (P = 0.020; 78% versus 62%). For patients with PCNSL, univariate analysis showed that patients with BCL-6 expression had a trend towards longer survival (P = 0.073; median survival, 25.3 versus 7.3 months), and multivariate analysis showed BCL-6 was an independent prognostic factor (P = 0.026). For patients with NL, both of univariate (P = 0.003) and multivariate analyses (P = 0.002) showed that GCB was significantly associated with favorable survival. CONCLUSION: The higher frequency of non-GCB subclassification, which was mainly contributed by nuclear MUM-1 expression in PCNSL implies that it has a more differentiated cellular origin than NL. BCL-6 expression in patients with PCNSL and GCB subgroup in patients with NL were favorable prognostic factors.     

The GCB subtype of diffuse large B-cell lymphoma is less frequent in Asian countries

Patients with the germinal center B-cell-like (GCB) subtype of diffuse large B-cell lymphoma (DLBCL) have a significantly better survival rate than those with non-GCB DLBCL. Several studies have examined the proportions of GCB and non-GCB subtypes in large series of DLBCL patients, but it remains unclear if these proportions are the same in different countries. We performed an immunohistochemical analysis of the numbers of GCB and non-GCB subtypes in a large number of patients with DLBCL in Japan and compared the results with literature data for other countries. We found that 71 of 248 patients (29%) had the GCB phenotype and 177 patients (71%) had the non-GCB subtype of DLBCL among our patient population. Assessment of data collected from other studies showed that 31% of DLBCL patients (102/330) have the GCB subtype in Asian countries, but 50% (206/416) express GCB phenotypes in Western countries; based on these data, the occurrence of the GCB subtype of DLBCL was significantly less in Asian countries (p<0.001). Since patients with the GCB phenotype of DLBCL have better survival, future studies of DLBCL should recognize the difference in the proportions of GCB and non-GCB subtypes of DLBCL between Asian and Western populations.     

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.     

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.     

bcl-2与NF-κB／p65在弥漫性大B细胞淋巴瘤不同亚型中表达的意义

 目的　探讨bcl-2与NF-κB／p65蛋白在弥漫性大B细胞淋巴瘤（DLBCL）不同亚型中的表达及其意义。方法　用免疫组织化学方法检测DLBCL患者CD10、bcl-6、MUM-1蛋白的表达,以Hans等的分型原则将其划分为GCB和非GCB／ABC亚型,同时标记bcl-2与NF-κB／p65抗体,比较bcl-2与NF-κB／p65蛋白在GCB和ABC亚型中的表达情况并分析二者与DLBCL两种主要亚型生存率的相关性。结果　bcl-2与NF-κB／p65蛋白在DLBCL中的表达率为67.1 %和77.1 %, 二者表达呈正相关;GCB亚型中bcl-2与NF-κB／p65的表达率分别为52.0 %和56.0 %,ABC亚型中bcl-2与NF-κB／p65蛋白的表达率分别为75.6 %和88.9 %,ABC亚型中bcl-2与NF-κB／p65的表达率高于GCB亚型;在GCB亚型中,bcl-2与NF-κB／p65蛋白的表达与总生存率无显著的相关性,而在ABC亚型DLBCL中,bcl-2与NF-κB／p65蛋白的表达与生存率密切相关。结论　仅在ABC亚型DLBCL中,bcl-2与NF-κB／p65蛋白的表达是影响预后的重要不利因素,因此,需在DLBCL亚分型的基础上评估bcl-2与NF-κB／p65蛋白表达的预后意义。     

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。     

Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma.

Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed biologically and prognostically distinct subgroups: germinal center B-cell-like (GCB), activated B-cell-like (ABC) and primary mediastinal (PM) DLBCL. The BCL6 gene is often translocated and/or mutated in DLBCL. Therefore, we examined the BCL6 molecular alterations in these DLBCL subgroups, and their impact on BCL6 expression and BCL6 target gene repression. BCL6 translocations at the major breakpoint region (MBR) were detected in 25 (18.8%) of 133 DLBCL cases, with a higher frequency in the PM (33%) and ABC (24%) subgroups than in the GCB (10%) subgroup. Translocations at the alternative breakpoint region (ABR) were detected in five (6.4%) of 78 DLBCL cases, with three cases in ABC and one case each in the GCB and the unclassifiable subgroups. The translocated cases involved IgH and non-IgH partners in about equal frequency and were not associated with different levels of BCL6 mRNA and protein expression. BCL6 mutations were detected in 61% of DLBCL cases, with a significantly higher frequency in the GCB and PM subgroups (>70%) than in the ABC subgroup (44%). Exon-1 mutations were mostly observed in the GCB subgroup. The repression of known BCL6 target genes correlated with the level of BCL6 mRNA and protein expression in GCB and ABC subgroups but not with BCL6 translocation and intronic mutations. No clear inverse correlation between BCL6 expression and p53 expression was observed. Patients with higher BCL6 mRNA or protein expression had a significantly better overall survival. The biological role of BCL6 in translocated cases where repression of known target genes is not demonstrated is intriguing and warrants further investigation.     

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。      

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.     

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.     

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。     

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.     

叉头框转录蛋白1在弥漫性大B细胞淋巴瘤中的表达及预后意义

目的 探讨叉头框转录蛋白1（FOXP1）在弥漫性大B细胞淋巴瘤（DLBCL）中的表达及其与DLBCL临床病理特征和预后的关系。方法 用免疫组织化学En Vision法检测85例DLBCL组织中FOXP1蛋白的表达情况,并分析FOXP1与临床病理特征及预后的关系。结果 85例DLBCL组织中FOXP1的阳性表达率为71.8％（61／85）,FOXP1表达与年龄、PS评分、乳酸脱氢酶（LDH）水平、国际预后指数评分、病理类型密切相关（P＜0.05）。在生发中心型（GCB）DLBCL中FOXP1阳性和阴性表达者的无病生存期（PFS）为13个月和44个月（P=0.002）,总生存期（OS）为28个月和50个月（P=0.003）;而在非生发中心型（non-GCB）中FOXP1表达与生存预后无关（P＞0.05）。单因素分析显示分期、LDH水平、有无B症状以及FOXP1表达与DLBCL患者的PFS和OS均相关（P＜0.05）,Cox多因素回归分析显示分期（95%CI：1.410~4.415,P=0.02）和FOXP1表达（95%CI：0.143～0.734,P=0.007）是PFS的独立预测因素。 结论 FOXP1蛋白有可能是DLBCL的一个重要的预后指标,尤其在GCB型DLBCL中FOXP1蛋白阳性表达提示预后不佳。     

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.     

CD138在弥漫大B细胞淋巴瘤免疫分型构建及预后评估中的意义

目的 探讨CD138的表达及不同免疫分型方法与弥漫大B细胞淋巴瘤(DLBCL)患者预后的关系.方法 收集106例DLBCL组织标本,应用免疫组化EnVision法检测CD138、CD10、MUM1及bcl-6的表达.基于免疫标记结果,根据4种不同免疫分型方法对106例患者进行分型,比较各亚型患者的预后,分析不同免疫分型方法对DLBCL患者预后的影响.结果 106例组织标本中,CD20均为弥漫阳性,CD3均为阴性,CD10的阳性率为21.7%,bcl-6的阳性率为26.4%,MUM1的阳性率为56.6%,CD138的阳性率为15.1%.其中CD10和bcl-6阳性者总生存期长于阴性者(P=0.001,P=0.041),而CD138阳性者总生存期短于阴性者(P=0.003).多因素Cox回归分析显示,ECOG评分、Hans分型、Colomo分型分别为DLBCL患者生存期(OS)和无进展生存期(PFS)的独立影响因素,两种免疫分型方法相对于OS的OR值(0.259和0.255)和PFS的OR值(0.248和0.244)接近.结论 Hans分型和Colomo分型均与DLBCL患者的预后有关,且对预后的影响力相近,CD138的表达对DLBCL患者预后的预测意义不大.

Abstract：

Objective The purpose of this study was to classify the diffuse large B-cell lymphoma (DLBCL) into different prognostic subgroups according to four different detection methods of the expression of CD138,CD10,bcl-6,and MUM1.In particular to investigate the significance of CD138 in immunohistochemical profiles and its correlation with prognosis in DLBCL. Methods Immunohistochemical EnVision method was used to detect the expression of CD138,CD10,bcl-6 and MUM1 in 106 cases of DLBCL and reconstructed into four different subtyping algorithms.Algorithm-1,according to the expression of CD10,bcl-6 and MUM1,the cases were assigned to GCB and non-GCB groups.Algorithm-2,according to the expression of CD138,CD10,bcl-6 and MUM1,the cases were assigned to A,B,C,D groups.Algorithm-3,according to the expression of CD10 and MUM1,the cases were assigned to GCB and non-GCB groups.Algorithm-4,according to the expression of CD138,CD10,bcl-6 and MUM1,the cases were assigned to GCB and non-GCB groups.Following up was included as well.Statistical analysis was performed using the SPSS 13.0 and differences were considered significant at P ＜0.05. Results CD138,MUM1,CD10 and bcl-6 were positive in 15.1%(16/106),56.6%(60/106),21.7(23/106) and 26.4%(28/106),respectively.The expression of CD10 and bcl-6 was associated with favorable OS(P =0.001 and 0.041,respectively),whereas the expression of CD138 was associated with unfavorable OS(P =0.003).Using multivariate Cox proportional hazards regression analysis,algorithm-1 and-4 were almost at the same level for prognosis of OS(OR = 0.259,0.255) and PFS(OR = 0.248,0.244). Conclusions Both Hans's algorithm and Colombo's algorithm including CD138 detection are associated with the prognosis of DLBCL patients.The two algorithms have similar OR value according to Cox analysis.However,positive expression of CD138 is of minor significance in prediction of the prognosis in DLBCL patients.     

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。      

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。