Histologic and Immunohistologic Findings and Prognosis of 40 Cases of Gastric Large B-Cell Lymphoma

Takeshita, Morishige; Iwashita, Akinori; Kurihara, Kenji; Izutsu, Koji; Higashi, Hidefumi; Udoh, Toshihiro; Kikuchi, Masahiro

doi:10.1097/00000478-200012000-00008

Cited by 65 publications

(34 citation statements)

References 17 publications

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“…Some studies using immunohistochemical methods have found CD10 expression to be associated with significantly improved OS. 20,23,28,38 Likewise, we found that CD10 expression predicts for better OS. However, given the variability of outcomes in these retrospective studies, it is doubtful that CD10 alone can be used to predict survival in DLBCL.…”

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confidence: 51%

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Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray

Hans

Weisenburger

Greiner

et al. 2004

Blood

3,633

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Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important subgroups with germinal center Bcell-like (GCB), activated B-cell-like (ABC), and type 3 gene expression profiles using a cDNA microarray. Tissue microarray (TMA) blocks were created from 152 cases of DLBCL, 142 of which had been successfully evaluated by cDNA microarray (75 GCB, 41 ABC, and 26 type 3). Sections were stained with antibodies to CD10, bcl-6, MUM1, FOXP1, cyclin D2, and bcl-2. Expression of bcl-6 (P < .001) or CD10 (P ‫؍‬ .019) was associated with better overall survival (OS), whereas expression of MUM1 (P ‫؍‬ .009) or cyclin D2 (P < .001) was associated with worse OS. Cases were subclassified using CD10, bcl-6, and MUM1 expression, and 64 cases (42%) were considered GCB and 88 cases (58%) non-GCB. The 5-year OS for the GCB group was 76% compared with only 34% for the non-GCB group (P < .001), which is similar to that reported using the cDNA microarray. Bcl-2 and cyclin D2 were adverse predictors in the non-GCB group. In multivariate analysis, a high International Prognostic Index score (3-5) and the non-GCB phenotype were independent adverse predictors (P < .0001). In summary, immunostains can be used to determine the GCB and non-GCB subtypes of DLBCL and predict survival similar to the cDNA microarray. IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and accounts for 30% to 40% of new diagnoses. 1,2 However, DLBCL is heterogeneous both clinically and morphologically. Despite the use of anthracycline-based chemotherapy, durable remissions are achieved in only 40% to 50% of patients. 2 Therefore, it is important to identify at diagnosis those patients who may benefit from more aggressive or experimental therapies.Currently, the prognosis of patients with DLBCL is estimated using the clinical parameters of the International Prognostic Index (IPI). 3 However, these clinical parameters reflect a mixture of underlying biologic or genetic differences. In an attempt to elucidate these underlying factors, the prognostic value of numerous individual proteins has been studied by immunoperoxidase and molecular techniques. However, these studies have yielded conflicting results, and none have been validated in a large prospective trial. Therefore, in contrast to the IPI, these individual markers are generally not used in clinical practice for selecting therapy or predicting prognosis.Using a cDNA microarray, DLBCL can be divided into prognostically significant subgroups with germinal center B-celllike (GCB), activated B-cell-like (ABC), or type 3 gene expression profiles. 35,36 The GCB group has a significantly better survival than the ABC group. The type 3 group is heterogeneous and not well defined, but has a poor outcome similar to the ABC group. Another study using an oligonucleotide array has demonstrated that DLBCL can be divided into 2 molecularly distinct populations (cured and fatal/refractory). 37 Because this technology is expensive and not generally available, a sim...

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supporting

confidence: 51%

“…18 Other studies have reported that bcl-6 expression predicts for better OS. 20,24,30 We found that bcl-6 expression by immunohistochemistry predicts for both better OS and EFS. Furthermore, bcl-6, in conjunction with CD10 and MUM1, is a useful marker to identify the GCB phenotype.…”

mentioning

confidence: 71%

Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray

Hans

Weisenburger

Greiner

et al. 2004

Blood

3,633

138

3,287

View full text Add to dashboard Cite

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“…It is unclear how these studies apply to the assessment of gastric DLBCL, which shows much better prognosis than nodal disease, perhaps because most cases are of early stage (I/II). In gastric DLBCL, only three studies have shown the prognostic value of immunoexpression of CD10 (41,42), BCL6 (7,41), or GCB/non-GCB phenotyping (7) in a relatively small number of cases. In our large study, classification of all cases by GCB/non-GCB subgroup or by expression of CD10, BCL6, or MUM1 did not correlate with OS or EFS.…”

Section: Discussionmentioning

confidence: 99%

Translocations Involving the Immunoglobulin Heavy Chain Gene Locus Predict Better Survival in Gastric Diffuse Large B-Cell Lymphoma

Nakamura

Bacon

et al. 2008

Clinical Cancer Research

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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.Primary gastric lymphoma is the most common extranodal lymphoma (1). Histologically, the majority of gastric lymphoma comprises extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphoma (DLBCL). In gastric MALT lymphoma, t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/ BCL10-IGH , t(14;18)(q32;q21)/IGH-MALT1 , and t(3;14) (p14;q32)/FOXP1-IGH have been identified at variable frequencies, and the clinical effect of t(11;18)(q21;q21) is wellcharacterized (1, 2). In contrast, the molecular pathogenesis of gastric DLBCL is poorly understood, although it is generally believed that many cases arise by transformation of MALT lymphoma.Across all sites, DLBCL is the most common type of nonHodgkin lymphoma. Importantly, DLBCL shows marked heterogeneity in morphology, genetics, and clinical features (3). Translocations involving the immunoglobulin heavy chain gene (IGH) locus are frequent in DLBCL and are most commonly

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“…[24][25][26] Many markers have been used to segregate the different groups in regard to their cell of origin and the impact on prognosis and clinical behavior. [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] However, it is now accepted that the expression of CD10, Bcl-6 and MUM1 can be used to subclassify diffuse large B-cell lymphoma into germinal center B-cell-like and nongerminal center B-cell-like groups. Thus, it has been shown that the combined expression, or lack thereof, of CD10, Bcl-6 and MUM1 is the best immunohistochemical approach to subclassify diffuse large B-cell lymphoma into two major prognostically different categories using the method of Hans et al 26 Those with CD10 and/or Bcl-6 expression and lack of MUM1 have a germinal center B-cell-like phenotype and better overall survival; the other group, with a CD10-negative/Bcl-6-negative/MUM1-positive immunophenotype, has nongerminal center B-cell-like differentiation and worse overall survival.…”

Section: Discussionmentioning

confidence: 99%

Primary testicular diffuse large B-cell lymphoma belongs to the nongerminal center B-cell-like subgroup: a study of 18 cases

et al. 2006

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The most common type of primary testicular lymphoma is diffuse large B-cell type, which has the potential for aggressive clinical behavior. Diffuse large B-cell lymphoma can be further subclassified into two major prognostic categories: germinal center B-cell-like and nongerminal center B-cell-like. Such distinction is made possible using the immunohistochemical expression of CD10, Bcl-6 and MUM1. The aim of this study was to stratify primary testicular lymphoma of the diffuse large B-cell type according to this scheme. Immunohistochemical stains for CD10, Bcl-6 and MUM1 were performed on 18 cases of primary testicular lymphoma of diffuse large B-cell type. Subclassification was carried out as previously described where CD10 and/or Bcl-6 positivity and negativity for MUM1 were considered indicative of germinal center B-cell-like type and the opposite expression as nongerminal center B-cell-like type. The proliferative activity was determined using immunostaining with the Ki-67 antibody. Of 18 cases, 16 (89%) were found to belong to the nongerminal center B-cell-like type. Two cases (11%) were classified as germinal center B-cell-like type; one had a CD10-positive, Bcl-6-positive and MUM1-negative profile, and the other was CD10 negative, Bcl-6 positive and MUM1 negative. The former occurred in a 38-year-old patient who was human immunodeficiency virus positive. All the cases expressed high proliferative activity (Z50% Ki-67 labeling). We conclude that most (89%) primary testicular lymphomas of the diffuse large B-cell type belong to the nongerminal center B-cell-like subgroup and have high proliferative activity.

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Histologic and Immunohistologic Findings and Prognosis of 40 Cases of Gastric Large B-Cell Lymphoma

Cited by 65 publications

References 17 publications

Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray

Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray

Translocations Involving the Immunoglobulin Heavy Chain Gene Locus Predict Better Survival in Gastric Diffuse Large B-Cell Lymphoma

Primary testicular diffuse large B-cell lymphoma belongs to the nongerminal center B-cell-like subgroup: a study of 18 cases

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