Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas.

Mutation of the ARID1A gene and loss of the corresponding protein BAF250a has recently been described as a frequent event in clear cell and endometrioid carcinomas of the ovary. To determine whether BAF250a loss is common in other malignancies, immunohistochemistry (IHC) for BAF250a was performed on tissue microarrays (TMAs) in more than 3000 cancers, including carcinomas of breast, lung, thyroid, endometrium, kidney, stomach, oral cavity, cervix, pancreas, colon and rectum, as well as endometrial stromal sarcomas, gastrointestinal stromal tumours, sex cord-stromal tumours and four major types of lymphoma (diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, mantle cell lymphoma and follicular lymphoma). We found that BAF250a loss is frequent in endometrial carcinomas but infrequent in other types of malignancies, with loss observed in 29% (29/101) of grade 1 or 2 and 39% (44/113) of grade 3 endometrioid carcinomas of the endometrium, 18% (17/95) of uterine serous carcinomas and 26% (6/23) of uterine clear cell carcinomas.

Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project.

Few large, international series of enteropathy-associated T-cell lymphoma (EATL) have been reported. We studied a cohort of 62 patients with EATL among 1153 patients with peripheral T-cell or natural killer (NK)-cell lymphoma from 22 centers worldwide. The diagnosis was made by a consensus panel of 4 expert hematopathologists using World Health Organization (WHO) criteria.

High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy.

Background: Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown.

Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium.

The Lunenburg Lymphoma Biomarker Consortium (LLBC) evaluated the prognostic value of IHC biomarkers in a large series of patients with diffuse large B-cell lymphoma (DLBCL). Clinical data and tumor samples were retrieved from 12 studies from Europe and North America, with patients treated before or after the rituximab era. Using tissue microarrays from 1514 patients, IHC for BCL2, BCL6, CD5, CD10, MUM1, Ki67, and HLA-DR was performed and scored according to previously validated protocols.

MicroRNAs are independent predictors of outcome in diffuse large B-cell lymphoma patients treated with R-CHOP.

Purpose: Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict patients' outcome. However, even these predictors are not capable of unambiguously identifying outcome, suggesting that additional biomarkers might improve their predictive power.

Peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive diseases associated with poor outcome. Studies that focus specifically on PTCL are emerging, with the ultimate goal of improved understanding of disease biology and the development of more effective therapies. However, one of the difficulties in classifying and studying treatment options in clinical trials is the rarity of these subtypes.

MYC and aggressive B-cell lymphomas.

Rearrangement of the proto-oncogene MYC leads to MYC protein deregulation and is an important driver of oncogenic transformation. MYC rearrangement is a recurring genetic abnormality in several aggressive B-cell lymphomas including: Burkitt lymphoma, diffuse large B-cell lymphoma; B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma; rare de novo acute lymphoblastic lymphoma/leukemia, transformed follicular lymphoma, and plasmablastic lymphoma. Important distinctions in the role of MYC in these tumors likely reflect whether it is a primary or secondary genetic event.

Diffuse large B-cell lymphoma with involvement of the kidney: outcome and risk of central nervous system relapse.

Background: Renal involvement is uncommon in diffuse large B-cell lymphoma. Recent data suggest that it is an independent risk factor for central nervous system relapse. We reviewed the clinical features, risk of central nervous system involvement, and survival of patients with diffuse large B-cell lymphoma with involvement of the kidney at diagnosis.

Molecular pathogenesis of Hodgkin's lymphoma: increasing evidence of the importance of the microenvironment.

Hodgkin's lymphoma (HL) represents the most common subtype of malignant lymphoma in young people in the Western world. Most patients can be cured with modern treatment strategies, although approximately 20% will die after relapse or progressive disease. The histologic hallmark of the disease is the presence of the characteristic Hodgkin Reed-Sternberg (HRS) cells in classical HL and so-called lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant HL.

Genomic profiles of MALT lymphomas: variability across anatomical sites.

MALT lymphomas present common features, but important differences are associated with involvement of specific anatomical sites, many likely contributing to the biology. To test the existence of genetic alterations specific for primary anatomical sites of involvement, genomic profiles obtained with high-density arrays were analyzed in 130 MALT lymphomas across a spectrum of anatomic sites. Trisomies 3 and 18 and del(6q23) occurred at a similar frequency.

Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP.

Purpose: In diffuse large B-cell lymphoma (DLBCL), prior studies suggest that concordant bone marrow involvement with DLBCL portends a poorer prognosis, whereas discordant bone marrow involvement with small B-cell lymphoma does not. We examined the significance of bone marrow involvement in patients treated in the current era of therapy including rituximab.

Patients And Methods: We performed a retrospective analysis of the prognostic impact of bone marrow involvement in an unselected population of patients with newly diagnosed DLBCL treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in British Columbia and Auckland, New Zealand, with complete clinical information and evaluable staging bone marrow biopsies.

MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers.

Chromosomal translocations are critically involved in the molecular pathogenesis of B-cell lymphomas, and highly recurrent and specific rearrangements have defined distinct molecular subtypes linked to unique clinicopathological features. In contrast, several well-characterized lymphoma entities still lack disease-defining translocation events. To identify novel fusion transcripts resulting from translocations, we investigated two Hodgkin lymphoma cell lines by whole-transcriptome paired-end sequencing (RNA-seq).

Accurate classification of diffuse large B-cell lymphoma into germinal center and activated B-cell subtypes using a nuclease protection assay on formalin-fixed, paraffin-embedded tissues.

Classification of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin (COO) subtypes based on gene expression profiles has well-established prognostic value. These subtypes, termed germinal center B cell (GCB) and activated B cell (ABC) also have different genetic alterations and overexpression of different pathways that may serve as therapeutic targets. Thus, accurate classification is essential for analysis of clinical trial results and planning new trials by using targeted agents.

A phase II study of bortezomib and gemcitabine in relapsed mantle cell lymphoma from the National Cancer Institute of Canada Clinical Trials Group (IND 172).

Bortezomib and gemcitabine have each shown activity as single agents in mantle cell lymphoma (MCL), which is incurable. The purpose of this phase II study was to determine the efficacy and safety of the previously unstudied combination of bortezomib and gemcitabine in patients with relapsed or refractory MCL. Patients were eligible if they had relapsed MCL with 1-3 prior therapies.

Immunoexpression of Survivin in non-neoplastic lymphoid tissues and malignant lymphomas using a new monoclonal antibody reactive on paraffin sections.

Survivin is a member of the inhibitor of apoptosis gene family, which is also implicated in mitosis regulation. Most reports in the literature impute poor prognosis to neoplasms with overexpression of this protein. The purpose of the present study is to validate and compare the immunohistochemical reactivity of malignant lymphomas and reactive lymphoid tissue using a new mouse monoclonal antibody to Survivin produced in our laboratory, 6-78.

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project.

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified.

Molecular characteristics of mantle cell lymphoma presenting with clonal plasma cell component.

The normal counterparts of mantle cell lymphoma (MCL) are naive, quiescent B cells that have not been processed through the germinal center (GC). For this reason, although lymphomas arising from GC or post-GC B cells often exhibit plasmacytic differentiation, MCL rarely presents with plasmacytic features. Seven cases of MCL with a monotypic plasma cell (PC) population were collected from 6 centers and were studied by immunohistochemistry, fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms analysis, capillary gel electrophoresis, and restriction fragment length polymorphism of immunoglobulin heavy chain analysis of microdissections of each of the MCL and PC populations to assess their clonal relationship.

Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation.

Next-generation sequencing of follicular lymphoma and diffuse-large B-cell lymphoma has revealed frequent somatic, heterozygous Y641 mutations in the histone methyltransferase EZH2. Heterozygosity and the presence of equal quantities of both mutant and wild-type mRNA and expressed protein suggest a dominant mode of action. Surprisingly, B-cell lymphoma cell lines and lymphoma samples harboring heterozygous EZH2(Y641) mutations have increased levels of histone H3 Lys-27-specific trimethylation (H3K27me3).

Oncogenically active MYD88 mutations in human lymphoma.

The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours.

The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab.

The cellular composition of the tumor microenvironment may affect survival in diffuse large B-cell lymphoma (DLBCL). We performed immunostains for 2 stromal cell markers, CD68 and SPARC (secreted protein, acidic and rich in cysteine), in 262 patients with DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapies. Patients with any SPARC+ cells in the microenvironment had a significantly longer overall survival, and patients with high SPARC positivity in the microenvironment also had a significantly longer event-free survival.

Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab.

Purpose: Patients with diffuse large B-cell lymphoma (DLBCL) can be divided into prognostic groups based on the cell of origin of the tumor as determined by microarray analysis. Various immunohistochemical algorithms have been developed to replicate these microarray results and/or stratify patients according to survival. This study compares some of those algorithms and also proposes some modifications.

Mantle cell lymphoma: report of the 2010 Mantle Cell Lymphoma Consortium Workshop.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma typically characterized by cyclin D1 overexpression as result of the t(11;14) translocation. MCL is biologically and clinically heterogeneous and frequently involves extranodal dissemination. Although MCL is incurable with current therapies, with the exception of allogeneic stem cell transplant, recent advances are improving long-term outcomes in MCL.