MUM1

Gene Summary

Gene:MUM1; melanoma associated antigen (mutated) 1
Aliases: MUM-1, EXPAND1, HSPC211
Location:19p13.3
Summary:-
Databases:VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:PWWP domain-containing protein MUM1
HPRD
Source:NCBIAccessed: 16 March, 2015

Ontology:

What does this gene/protein do?
Show (5)

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 16 March 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Chromosome 14
  • Mutation
  • Sensitivity and Specificity
  • Testicular Cancer
  • Germinal Center
  • B-Lymphocytes
  • Cell Differentiation
  • Chromosome 18
  • Phenotype
  • BAD
  • Cancer Gene Expression Regulation
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Childhood Cancer
  • Chromosome Aberrations
  • BCL2 protein
  • Multiple Myeloma
  • Diffuse Large B-Cell Lymphoma
  • Young Adult
  • Gene Rearrangement
  • Staging
  • Adolescents
  • Proto-Oncogene Proteins c-bcl-6
  • Immunohistochemistry
  • Immunophenotyping
  • FISH
  • Follicular Lymphoma
  • Tissue Array Analysis
  • Interferon Regulatory Factors
  • B-Cell Lymphoma
  • Stomach
  • Chromosome 19
  • Polymerase Chain Reaction
  • Immunoglobulin Heavy Chains
  • DNA-Binding Proteins
  • Chromosome 6
  • Neprilysin
  • Oligonucleotide Array Sequence Analysis
  • Gene Expression Profiling
Tag cloud generated 16 March, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (3)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: MUM1 (cancer-related)

Al-Kawaaz M, Mathew S, Liu Y, et al.
Cyclin D1-positive diffuse large B-cell lymphoma with IGH-CCND1 translocation and BCL6 rearrangement: a report of two cases.
Am J Clin Pathol. 2015; 143(2):288-99 [PubMed] Related Publications
OBJECTIVES: To demonstrate and confirm the existence of cyclin D1-positive diffuse large B-cell lymphoma (DLBCL) with IGH-CCND1 rearrangement and discuss the rationale of differentiating this entity from blastoid and pleomorphic variants of mantle cell lymphoma (MCL).
METHODS: Two cyclin D1-positive lymphomas with morphologic features of DLBCL and IGH-CCND1 translocations were characterized with respect to clinical features, as well as morphologic, immunophenotypic, cytogenetic, and molecular findings.
RESULTS: The large tumor cells were CD20+, CD5-, CD10-, BCL6+, MUM1+, and cyclin D1+ in both cases. SOX11 was negative. Epstein-Barr virus-encoded RNA in situ hybridization demonstrated diffuse positivity in case 1. BCL6 and IGH-CCND1 rearrangements were identified by fluorescence in situ hybridization in both cases. Specifically, the diagnosis of a relapsed DLBCL with acquisition of IGH-CCND1 was rendered for case 1, molecularly confirmed by the detection of identical monoclonal IGH rearrangements between the initial diagnostic DLBCL and relapse lymphoma.
CONCLUSIONS: Our study demonstrates convincingly that IGH-CCND1 rearrangement leading to cyclin D1 overexpression can occur in DLBCL and pose a potential diagnostic pitfall, requiring thorough knowledge of the clinicopathologic findings to allow accurate discrimination from a blastoid or pleomorphic MCL. The coexistence of IGH-CCND1 and IGH-BCL6 rearrangements suggest that BCL6 and cyclin D1 may cooperate in the pathogenesis of DLBCL.

Gheith S, Cornfield D, Chen W, et al.
Immunoblastic follicular lymphoma: a very unusual transformation of low-grade follicular lymphoma.
Hum Pathol. 2014; 45(11):2359-63 [PubMed] Related Publications
A 73-year-old man, in clinical remission 17 years after radiation therapy for a localized low-grade follicular lymphoma (FL), developed extensive lymphadenopathy, ascites, and splenomegaly with splenic masses. Axillary lymph node biopsy showed FL composed of nodules of centrocytes side by side with nodules of immunoblasts rather than centroblasts. Immunophenotyping revealed conventional FL markers (BCL-2, BCL-6, and CD10) as well as MUM-1 in the immunoblastic component, suggesting postgerminal center differentiation. Fluorescence in situ hybridization showed t(14;18) in both centrocytic and immunoblastic components and a copy gain of BCL-6 predominantly in the immunoblastic component. Areas of centrocytic and of immunoblastic nodules were macrodissected separately and underwent molecular evaluation for immunoglobulin heavy chain gene rearrangement. Identical base-pair peaks were found, attesting to their clonal identity. This case represents a very unusual example of transformation of a low-grade FL to a nodular immunoblastic FL.

Guo Y, Takeuchi I, Karnan S, et al.
Array-comparative genomic hybridization profiling of immunohistochemical subgroups of diffuse large B-cell lymphoma shows distinct genomic alterations.
Cancer Sci. 2014; 105(4):481-9 [PubMed] Related Publications
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.

Somja J, Bisig B, Bonnet C, et al.
Peripheral T-cell lymphoma with t(6;14)(p25;q11.2) translocation presenting with massive splenomegaly.
Virchows Arch. 2014; 464(6):735-41 [PubMed] Related Publications
Recurrent chromosomal translocations associated to peripheral T-cell lymphomas (PTCL) are rare. Here, we report a case of PTCL, not otherwise specified (NOS) with the karyotype 46,Y,add(X)(p22),t(6;14)(p25;q11) and FISH-proved breakpoints in the IRF4 and TCRAD loci, leading to juxtaposition of both genes. A 64-year-old male patient presented with mild cytopenias and massive splenomegaly. Splenectomy showed diffuse red pulp involvement by a pleomorphic medium- to large-cell T-cell lymphoma with a CD2+ CD3+ CD5- CD7- CD4+ CD8+/- CD30- TCRbeta-F1+ immunophenotype, an activated cytotoxic profile, and strong MUM1 expression. The clinical course was marked by disease progression in the bone marrow under treatment and death at 4 months. In contrast with two t(6;14)(p25;q11.2)-positive lymphomas previously reported to be cytotoxic PTCL, NOS with bone marrow and skin involvement, this case was manifested by massive splenomegaly, expanding the clinical spectrum of PTCLs harboring t(6;14)(p25;q11.2) and supporting consideration of this translocation as a marker of biological aggressiveness.

Yang T, Zheng XF, Li M, et al.
Stimulation of osteogenic differentiation in stromal cells of giant cell tumour of bone by zoledronic acid.
Asian Pac J Cancer Prev. 2013; 14(9):5379-83 [PubMed] Related Publications
Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations (0 μM, 0.01 μM, 0.1 μM, 1 μM, 5 μM, 30 μM) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1 μM in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.

Coutinho R, Clear AJ, Owen A, et al.
Poor concordance among nine immunohistochemistry classifiers of cell-of-origin for diffuse large B-cell lymphoma: implications for therapeutic strategies.
Clin Cancer Res. 2013; 19(24):6686-95 [PubMed] Free Access to Full Article Related Publications
PURPOSE: The opportunity to improve therapeutic choices on the basis of molecular features of the tumor cells is on the horizon in diffuse large B-cell lymphoma (DLBCL). Agents such as bortezomib exhibit selective activity against the poor outcome activated B-cell type (ABC) DLBCL. In order for targeted therapies to succeed in this disease, robust strategies that segregate patients into molecular groups with high reliability are needed. Although molecular studies are considered gold standard, several immunohistochemistry (IHC) algorithms have been published that claim to be able to stratify patients according to their cell-of-origin and to be relevant for patient outcome. However, results are poorly reproducible by independent groups.
EXPERIMENTAL DESIGN: We investigated nine IHC algorithms for molecular classification in a dataset of DLBCL diagnostic biopsies, incorporating immunostaining for CD10, BCL6, BCL2, MUM1, FOXP1, GCET1, and LMO2. IHC profiles were assessed and agreed among three expert observers. A consensus matrix based on all scoring combinations and the number of subjects for each combination allowed us to assess reliability. The survival impact of individual markers and classifiers was evaluated using Kaplan-Meier curves and the log-rank test.
RESULTS: The concordance in patient's classification across the different algorithms was low. Only 4% of the tumors have been classified as germinal center B-cell type (GCB) and 21% as ABC/non-GCB by all methods. None of the algorithms provided prognostic information in the R-CHOP (rituximab plus cyclophosphamide-adriamycin-vincristine-prednisone)-treated cohort.
CONCLUSION: Further work is required to standardize IHC algorithms for DLBCL cell-of-origin classification for these to be considered reliable alternatives to molecular-based methods to be used for clinical decisions.

Richards KL, Motsinger-Reif AA, Chen HW, et al.
Gene profiling of canine B-cell lymphoma reveals germinal center and postgerminal center subtypes with different survival times, modeling human DLBCL.
Cancer Res. 2013; 73(16):5029-39 [PubMed] Free Access to Full Article Related Publications
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, and fewer than half of patients are cured with standard first-line therapy. To improve therapeutic options, better animal models that accurately mimic human DLBCL (hDLBCL) are needed. Canine DLBCL, one of the most common cancers in veterinary oncology, is morphologically similar to hDLBCL and is treated using similar chemotherapeutic protocols. With genomic technologies, it is now possible to molecularly evaluate dogs as a potential large-animal model for hDLBCL. We evaluated canine B-cell lymphomas (cBCL) using immunohistochemistry (IHC) and gene expression profiling. cBCL expression profiles were similar in many ways to hDLBCLs. For instance, a subset had increased expression of NF-κB pathway genes, mirroring human activated B-cell (ABC)-type DLBCL. Furthermore, immunoglobulin heavy chain ongoing mutation status, which is correlated with ABC/germinal center B-cell cell of origin in hDLBCL, separated cBCL into two groups with statistically different progression-free and overall survival times. In contrast with hDLBCL, cBCL rarely expressed BCL6 and MUM1/IRF4 by IHC. Collectively, these studies identify molecular similarities to hDLBCL that introduce pet dogs as a representative model of hDLBCL for future studies, including therapeutic clinical trials.

Reber R, Banz Y, Garamvölgyi E, et al.
Determination of the molecular subtypes of diffuse large B-cell lymphomas using immunohistochemistry: a case series from the Inselspital, Bern, and a critical appraisal of this determination in Switzerland.
Swiss Med Wkly. 2013; 143:w13748 [PubMed] Related Publications
The two major subtypes of diffuse large B-cell lymphoma (DLBCL) (germinal centre B-cell - like (GCB-DLBCL) and activated B-cell - like (ABC-DLBCL)) are defined by means of gene expression profiling (GEP). Patients with GCB-DLBCL survive longer with the current standard regimen R-CHOP than patients with ABC-DLBCL. As GEP is not part of the current routine diagnostic work-up, efforts have been made to find a substitute than involves immunohistochemistry (IHC). Various algorithms achieved this with 80-90% accuracy. However, conflicting results on the appropriateness of IHC have been reported. Because it is likely that the molecular subtypes will play a role in future clinical practice, we assessed the determination of the molecular DLBCL subtypes by means of IHC at our University Hospital, and some aspects of this determination elsewhere in Switzerland. The most frequently used Hans algorithm includes three antibodies (against CD10, bcl-6 and MUM1). From records of the routine diagnostic work-up, we identified 51 of 172 (29.7%) newly diagnosed and treated DLBCL cases from 2005 until 2010 with an assigned DLBCL subtype. DLBCL subtype information was expanded by means of tissue microarray analysis. The outcome for patients with the GCB subtype was significantly better compared with those with the non-GC subtype, independent of the age-adjusted International Prognostic Index. We found a lack of standardisation in the subtype determination by means of IHC in Switzerland and significant problems of reproducibility. We conclude that the Hans algorithm performs well in our hands and that awareness of this important matter is increasing. However, outside clinical trials, vigorous efforts to standardise IHC determination are needed as DLBCL subtype-specific therapies emerge.

Bisig B, de Reyniès A, Bonnet C, et al.
CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features.
Haematologica. 2013; 98(8):1250-8 [PubMed] Free Access to Full Article Related Publications
Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30(+) peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30(+) and CD30(-); anaplastic large cell lymphomas, ALK(+) and ALK(-)), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30(-) tumors, CD30(+) peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK(-) anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30(+) peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30(-) samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30(-) peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30(+) subgroups. In conclusion, we show molecular and phenotypic features common to CD30(+) peripheral T-cell lymphomas, and significant differences between CD30(-) and CD30(+) peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups.

Chang ST, Lu YH, Lu CL, et al.
Follicular lymphoma in Taiwan: a low frequency of t(14;18), with grade 3A tumours more closely related to grade 3B than to low-grade tumours.
Histopathology. 2013; 63(1):1-12 [PubMed] Related Publications
AIMS: To investigate t(14;18)/IGH-BCL2 in follicular lymphoma (FL) cases from Taiwan.
METHODS AND RESULTS: We retrospectively studied 93 consecutive cases, using immunohistochemistry and fluorescence in-situ hybridization (FISH). Fifty-nine (63%) tumours were low-grade (LG) and 34 (37%) were high-grade (HG; 24% FL3A and 13% FL3B). FISH showed IGH, BCL2 and BCL6 rearrangements in 59%, 47% and 11% of cases, respectively, and MYC rearrangement in 5% of FL3A tumours and 25% of FL3B tumours. The translocation partner of all BCL2 rearrangements was IGH, with IGH-BCL2 fusion in 63% of LG tumours and 18% of HG tumours. LG tumours were enriched with a CD10+/bcl-2+/MUM1- phenotype, and were frequently associated with BCL2 rearrangement but less commonly with BCL6 rearrangement. FL3A tumours were more closely related to FL3B tumours than to LG tumours in immunophenotype and genetic aberrations. There was no statistically significant difference between grade 1 and two tumours, between FL3A and FL3B tumours or between nodal and extranodal tumours in immunophenotypic or FISH findings. The cumulative survival rate was higher in LG FL patients with IGH-BCL2 translocation than in those without rearrangement.
CONCLUSIONS: In Taiwan, FL3A tumours were more closely related to FL3B tumours than to LG tumours, and a literature review showed that the frequency of t(14;18)/IGH-BCL2 in FL in Taiwan is among the lowest in the world.

Pillai RK, Sathanoori M, Van Oss SB, Swerdlow SH
Double-hit B-cell lymphomas with BCL6 and MYC translocations are aggressive, frequently extranodal lymphomas distinct from BCL2 double-hit B-cell lymphomas.
Am J Surg Pathol. 2013; 37(3):323-32 [PubMed] Related Publications
Double-hit (DH) lymphomas with MYC and either BCL2 (DH-BCL2/MYC) or BCL6 (DH-BCL6/MYC) rearrangements are considered very aggressive, many of which are now included in the category B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (DLBCL/BL). However, data describing the DH cases are largely based on DH-BCL2/MYC cases. To better characterize DH-BCL6/MYC cases, the clinical, morphologic, phenotypic, and cytogenetic features of 6 cases from University of Pittsburgh Medical Center and 17 cases from the Mitelman database were reviewed. In the University of Pittsburgh Medical Center cases, the median age was 83 years (range, 51 to 89 y) with 5/6 DLBCL/BL cases and 1 large B-cell lymphoma, not otherwise specified. Five of 6 had a germinal center phenotype, 1/6 was BCL2(+), and the median Ki-67 score was 98% (35% to 100%). The Mitelman DH-BCL6/MYC cases included 13 aggressive B-cell lymphomas (diagnosed as DLBCL-5, BL-5, BL-like lymphomas-2, and primary effusion lymphoma-1) and 4 other lymphoid/plasmacytic neoplasms. The median cytogenetic complexity score was 2.5 (range, 0 to 14) in 14 evaluable mature aggressive lymphomas with an immunoglobulin gene partner for MYC in 9/14 and for BCL6 in 7/14 cases. Ten of 13 cases involved extranodal extramedullary sites at presentation, and the median survival for the 10 patients with large cell neoplasms or BL and with available follow-up data was 9 months. Thus, DH-BCL6/MYC lymphomas are aggressive, frequently involve extranodal sites, and are often DLBCL/BL with a germinal center phenotype. Unlike DH-BCL2/MYC lymphomas, however, they are more likely to be CD10(-) but IRF4/MUM-1(+) (P=0.03) and, more like BL, only infrequently express BCL2 (P<0.001), and are cytogenetically less complex (P<0.04).

Paik JH, Go H, Nam SJ, et al.
Clinicopathologic implication of A20/TNFAIP3 deletion in diffuse large B-cell lymphoma: an analysis according to immunohistochemical subgroups and rituximab treatment.
Leuk Lymphoma. 2013; 54(9):1934-41 [PubMed] Related Publications
We analyzed the clinicopathologic implication of A20/tumor necrosis factor α-induced protein 3 deletion in diffuse large B-cell lymphoma (DLBCL) using fluorescence in situ hybridization, according to germinal center B-cell (GCB) versus non-GCB/activated B-cell (ABC) phenotypes and rituximab treatment. Excluding primary central nervous system (CNS) and Epstein-Barr virus (EBV)-positive lymphomas, 134 DLBCLs were analyzed. A20 was deleted in 23.1% (31/134) of DLBCLs including 21.6% (29/ 134) of monoallelic and 1.5% (2/134) of biallelic deletion, with no predilection for GCB versus non-GCB/ABC. In univariate analysis, A20 deletion was marginally associated with favorable prognosis in the rituximab-treated subgroup (n = 109; p = 0.0454), non-gastrointestinal lymphoma (n = 108; p = 0.0320) and nodal lymphoma (n = 46; p = 0.0411). In multivariate analysis in rituximab-treated DLBCL, MUM1 and international prognostic index (IPI) were independent prognostic factors (p = 0.021 [IPI]; p = 009 [MUM1]) with a marginally favorable prognostic effect for A20 deletion (p = 0.047). Taken together, A20 deletion was observed in similar frequencies in GCB and non-GCB/ABC, and was not a poor prognostic factor in DLBCL.

Nichele I, Zamò A, Bertolaso A, et al.
VR09 cell line: an EBV-positive lymphoblastoid cell line with in vivo characteristics of diffuse large B cell lymphoma of activated B-cell type.
PLoS One. 2012; 7(12):e52811 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: small B-cell neoplasms can show plasmacytic differentiation and may potentially progress to aggressive lymphoma (DLBCL). Epstein-Barr virus (EBV) infection may cause the transformation of malignant cells in vitro.
DESIGN AND METHOD: we established VR09 cell line with plasmacytic differentiation, obtained from a case of atypical, non-CLL B-cell chronic lymphoproliferative disease with plasmacytic features. We used flow cytometry, immunohistochemistry, polymerase chain reaction, cytogenetic analysis and florescence in situ hybridization in the attempt at thoroughly characterizing the cell line. We showed VR09 tumorigenic potential in vivo, leading to the development of activated DLBCL with plasmacytic features.
RESULTS: VR09 cells displayed plasmacytic appearance and grew as spherical tumors when inoculated subcutaneously into immunodeficient Rag2(-/-) γ-chain(-/-) mice. VR09 cell line and tumors displayed the phenotype of activated stage of B cell maturation, with secretory differentiation (CD19+ CD20+ CD79a+ CD79b+/- CD138+ cyclin D1- Ki67 80% IgM+ IgD+ MUM1+ MNDA+ CD10- CD22+ CD23+ CD43+ K+, λ- Bcl2+ Bcl6-) and they presented episomal EBV genome, chromosome 12 trisomy, lack of c-MYC rearrangement and Myd88 gene mutation, presence of somatic hypermutation in the VH region, and wild-type p53.
CONCLUSION: This new EBV-positive cell line may be useful to further characterize in vivo activated DLBCL with plasmacytic features.

Hashimoto M, Inaguma S, Kasai K, et al.
Plasmablastic lymphoma of the stomach in an HIV-negative patient.
Pathol Int. 2012; 62(11):763-70 [PubMed] Related Publications
Plasmablastic lymphoma (PBL) is a rare B-cell neoplasm with an aggressive clinical behavior that predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients. However, it has recently been recognized that PBLs can also affect individuals without HIV infection, and suggested that these neoplasms show different clinicopathological characteristics between HIV-positive and -negative patients. Herein we describe a case of gastric PBL in a female HIV-negative patient. The tumor was composed of a diffuse and cohesive proliferation of large neoplastic cells, which resembled immunoblasts or plasmablasts with a starry sky appearance. Immunophenotypically, the neoplastic cells were diffusely positive for CD138, MUM1, IgM, and BOB-1, and negative for CK, LCA, CD3, CD20, CD79a, Pax5, kappa, lambda, CD30, ALK, S-100, HMB-45, MPO, and HHV-8. The MIB-1 index was nearly 100%. Epstein-Barr virus-encoded RNA in situ hybridization was negative. A monoclonal immunoglobulin heavy chain gene rearrangement was detected in polymerase chain reaction (PCR) and heteroduplex analyses. A combination of PCR-based analysis of immunoglobulin gene rearrangement and immunohistochemistry can be useful to substantiate the diagnosis by utilizing routine paraffin-embedded tissue sections, because PBL in the setting of extra-oral localization and immunocompetence is a diagnostic challenge, given its rarity, morphology, and absence of CD20 expression.

Liu Q, Salaverria I, Pittaluga S, et al.
Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma.
Am J Surg Pathol. 2013; 37(3):333-43 [PubMed] Free Access to Full Article Related Publications
Follicular lymphoma (FL), a common lymphoma in adults, occurs rarely in pediatric and young adult patients. Most pediatric cases have been described as grade 3, but the criteria to distinguish the pediatric variant of FL (PFL) from usual FL (UFL) seen in adults are not well defined. We undertook a study of FL in patients under the age of 30. We identified 63 cases, which were analyzed by morphology, immunohistochemistry, and polymerase chain reaction analysis of IGH@ and IGK@ clonality. These data were correlated with clinical findings including stage, treatment, and outcome. Among the 63 cases, 34 cases were classified as PFL: 22 presenting in lymph nodes, 8 in the Waldeyer ring, and 4 in the testis. Clonal immunoglobulin gene rearrangement was detected in 97% of PFL cases, but fluorescence in situ hybridization analysis showed an absence of the BCL2/IGH@ translocation in all cases tested. Twenty-nine cases were classified as UFL, 28 of which presented in lymph nodes. The nodal PFLs were observed exclusively in male patients in both children and young adults with a median age of 15 years. They showed marked head/neck predilection, blastoid cytologic features with a high proliferation rate, lack of BCL2 protein and t(14;18), low clinical stage at presentation, and good prognosis. PFLs involving the Waldeyer ring were distinguished by MUM1 expression, 50% (3/6) of which carried IRF4 breaks. BCL2 expression was common (63%) in the absence of BCL2/IGH@ translocation. UFLs were more common in female patients, exclusively in young adults (median age, 24 y), with no cases reported in patients under the age of 18. Twenty-five of 29 cases were of grade 1-2, and 4 cases were classified as grade 3A. They exhibited a higher clinical stage at presentation. Eighty-three percent expressed BCL2. Our results indicate that histologic and immunophenotypic criteria can reliably separate PFL and UFL and that UFL is exceptionally rare in the pediatric age group. PFL associated with particular anatomic sites have distinctive features and should be evaluated separately in future clinical and biological studies.

Powell JR, Dojcinov S, King L, et al.
Prognostic significance of hypoxia inducible factor-1α and vascular endothelial growth factor expression in patients with diffuse large B-cell lymphoma treated with rituximab.
Leuk Lymphoma. 2013; 54(5):959-66 [PubMed] Related Publications
We evaluated hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression and their prognostic significance in diffuse large B-cell lymphoma (DLBCL). Expression of HIF-1α and VEGF was studied in 78 patients and results correlated with clinicopathological and prognostic data. HIF-1α and VEGF were expressed in 67% and 84% of patients, respectively, and a significant correlation was demonstrated between them (p < 0.001). Outcome was analyzed according to treatment. HIF-1α positive patients given rituximab demonstrated improved outcome, with 5-year overall survival of 72% for those receiving rituximab versus 65% for those not receiving rituximab, and 5-year progression-free survival (PFS) 76% versus 57%. No correlation was demonstrated between HIF-1α and other prognostic biomarkers including BCL6, CD10 and MUM-1. We demonstrated significantly improved PFS (p = 0.003) in patients receiving rituximab and showing BCL6 overexpression. The results confirm the significant association between HIF-1α and VEGF expression and suggest that HIF-1α expression is a favorable prognostic factor in patients with DLBCL treated with rituximab.

Takata K, Sato Y, Nakamura N, et al.
Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics.
Mod Pathol. 2013; 26(1):22-31 [PubMed] Related Publications
We have reported previously that duodenal follicular lymphoma (FL) is distinct from nodal FL and showed more resemblance to mucosa-associated lymphoid tissue lymphoma, and that FL frequently involved the duodenal second portion. In the present study, we examined duodenal FLs and gastric/colonic FLs to clarify the clinicopathological and immunological differences between the tumor types. We analyzed 8 samples of gastric FL, 17 of duodenal ones, and 5 of colonic/rectal ones, and characterized them by immunohistochemistry, immunogenotyping, and histology. Gastric and colonic FLs presented in submucosal to subserosal areas, whereas duodenal ones presented in the mucosal to submucosal layers. Immunohistochemical analysis revealed that duodenal FLs exhibited the following phenotypes: CD10 (+), B-cell lymphoma 2 (BCL-2) (+), BCL-6 (+), activation-induced cytidine deaminase (AID) (-), BACH2 (+), CD27 (+), MUM-1 (-), Blimp-1 (-), and loose CD21 network (duodenal pattern). Gastric/colonic FLs exhibited the following phenotypes: CD10 (+), BCL-2 (+), BCL-6 (+), AID (+), BACH2 (+), CD27 (-), MUM-1 (-), Blimp-1 (-), and a dense CD21 network (nodal pattern). Expression of AID and CD27 in lymphoma cells and the CD21 network pattern were considerably different between duodenal FLs and gastric/colonic ones. Moreover, in situ hybridization revealed that, in the duodenal FLs, BACH2 was expressed at the periphery of the tumor follicle and tumor villi. The number of immunoglobulin heavy-chain variable domains VH4 and VH5 were higher in duodenal follicular lymphomoas than in gastric FLs. The lymphoma cells of duodenal FLs are different from those of gastric/colonic FLs, and duodenal FL is distinct even within the gastrointestinal tract. Somatic hypermutation in immunoglobulin genes and CD27 expression are hallmarks of memory B cells. We suggest that duodenal FL cells are in the memory B-cell stage, and require BACH2 instead of AID for ongoing mutation.

Hong J, Park S, Park J, et al.
CD99 expression and newly diagnosed diffuse large B-cell lymphoma treated with rituximab-CHOP immunochemotherapy.
Ann Hematol. 2012; 91(12):1897-906 [PubMed] Related Publications
In order to evaluate prognostic value of CD99 expression in patients with diffuse large B-cell lymphoma (DLBCL) who underwent treatment with rituximab-CHOP immunochemotherapy, immunohistochemistry for CD99/CD10/BCL-2/BCL-6/MUM-1 was performed on nodal DLBCL specimens from 70 patients. Patients were classified as either germinal center B-cell (GCB) subtype or non-GCB subtype according to the Muris algorithm. A superior 2-year event-free survival (EFS) was observed in patients with the GCB subgroup, compared to those with the non-GCB subgroup (p = 0.034). The distribution of CD99 expression (29 patients; 41.4 %) did not show deviation according to subtype and was not prognostic for survival in the entire patient population. Among patients with the GCB subgroup, better EFS and overall survival (OS) were observed in CD99+ patients, compared to CD99- patients. Conversely, among patients with the non-GCB subgroup, inferior EFS and OS were reported in CD99+ patients. Superior 2-year EFS (p = 0.004) and 2-year OS (p = 0.003) were observed in patients with GCB/CD99+ and non-GCB/CD99- compared to the others, and the combination classification was found to be an independent prognostic factor.

Stacy RC, Jakobiec FA, Herwig MC, et al.
Diffuse large B-cell lymphoma of the orbit: clinicopathologic, immunohistochemical, and prognostic features of 20 cases.
Am J Ophthalmol. 2012; 154(1):87-98.e1 [PubMed] Related Publications
PURPOSE: To evaluate a series of orbital diffuse large B-cell lymphomas (DLBCL) for prognostic features and therapeutic outcomes.
DESIGN: Retrospective multicenter case study of clinical and immunohistochemical features of 20 patients.
METHODS: Clinical, histopathologic, and immunohistochemical features were correlated with outcomes. Immunohistochemistry for biomarkers including Bcl-6, CD5, CD10, CD20, FOXP1, GCET1, and MUM1 was performed to differentiate between 2 major genetic subtypes of DLBCL: activated B-cell-like (ABC) and germinal center B-cell-like (GCB).
RESULTS: Sixteen patients presented with unilateral and 4 with bilateral tumors. Three had bony erosion of the orbit on imaging studies. Of 14 patients with detailed follow-ups, 3 had a prior or concurrent lymphomatous disease; 8 had stage I disease (limited to the orbit) at presentation; and 3 were newly diagnosed with systemic (stage IV) DLBCL. Localized disease was treated with combined systemic chemotherapy, including rituximab and radiation with no deaths to date; there was 1 death related to systemic DLBCL. Clinical staging was the best predictive method and no immunohistochemical feature or subcategory (ABC vs GCB) correlated with outcome.
CONCLUSIONS: Primary orbital DLBCL has a more favorable prognosis than systemic DLBCL and may arise from a preexistent hematolymphomatous neoplasm (4 out of 20 cases). In our series, orbital DLBCL had a 57% likelihood of being restricted to the ocular adnexa. Clinical staging was more helpful in predicting outcome than any single immunohistopathologic feature or combination of biomarkers. Orbital radiation of 30 gray in conjunction with systemic chemotherapy with rituximab can achieve disease-specific survival approaching 100% in purely localized cases.

Visco C, Li Y, Xu-Monette ZY, et al.
Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study.
Leukemia. 2012; 26(9):2103-13 [PubMed] Free Access to Full Article Related Publications
Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.

Bisig B, Gaulard P, de Leval L
New biomarkers in T-cell lymphomas.
Best Pract Res Clin Haematol. 2012; 25(1):13-28 [PubMed] Related Publications
Peripheral T-cell lymphomas (PTCLs) are heterogeneous and uncommon malignancies characterized by an aggressive clinical course and a mostly poor outcome with current treatment strategies. The recent genome-wide molecular characterization of several entities has provided novel insights into their pathobiology and led to the identification of new biomarkers with diagnostic, prognostic or therapeutic implications for PTCL patients. Cell lineage and differentiation antigens (markers of γδ or NK lineage, of cytotoxicity, of follicular helper T cells) reflect the tumour's biological behaviour, and their detection in tissue samples may refine the diagnostic and prognostic stratification of the patients. Previously unrecognized gene rearrangements are being discovered (ITK-SYK translocation, IRF4/MUM1 and DUSP22 rearrangements), and may serve as diagnostic genetic markers. Deregulated molecules within oncogenic pathways (NF-κB, Syk, PDGFRα) and immunoreactive cell-surface antigens (CD30, CD52) have been brought to the fore as potential targets for guiding the development of novel therapies.

Katna R, Shet T, Sengar M, et al.
Clinicopathologic study and outcome analysis of thyroid lymphomas: experience from a tertiary cancer center.
Head Neck. 2013; 35(2):165-71 [PubMed] Related Publications
BACKGROUND: The aim of this study was to review clinicopathologic presentations of patients diagnosed with thyroid lymphomas at a tertiary cancer center. Thyroid lymphomas represent less than 2% of all lymphomas.
METHODS: The lymphoma clinic database was retrospectively reviewed to collect information on patients diagnosed with thyroid lymphomas. Tissue microarrays were constructed in 37 patients for evaluation of germinal center (CD10/bcl-6) and activated B-cell immunophenotype markers (FoxP1, Mum1).
RESULTS: During 2000 to 2010, 64 of 5668 patients registered at our lymphoma clinic were diagnosed with thyroid lymphoma (1.7%). Complete response (CR) to treatment was seen in 80.7%. The germinal center immunophenotype and activated B-cell immune phenotype did not influence the prognosis. FoxP1, however, was associated with poor treatment response and decreased survival.
CONCLUSIONS: Advanced International Prognostic Index (IPI) score and combined-modality treatment emerged as significant prognostic factors for treatment response and overall survival. Immunophenotype expression of FoxP1 carries a poor prognosis in diffuse large B-cell lymphoma as elsewhere.

Akyurek N, Uner A, Benekli M, Barista I
Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.
Cancer. 2012; 118(17):4173-83 [PubMed] Related Publications
BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases.
METHODS: Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients.
RESULTS: MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non-GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors.
CONCLUSIONS: Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis.

Wilkinson ST, Vanpatten KA, Fernandez DR, et al.
Partial plasma cell differentiation as a mechanism of lost major histocompatibility complex class II expression in diffuse large B-cell lymphoma.
Blood. 2012; 119(6):1459-67 [PubMed] Free Access to Full Article Related Publications
Loss of major histocompatibility complex class II (MHC II) expression is associated with poor patient outcome in diffuse large B-cell lymphoma (DLBCL). As MHC II molecules are lost with plasmacytic differentiation in normal cells, we asked whether MHC II loss in DLBCL is associated with an altered differentiation state. We used gene expression profiling, quantum dots, and immunohistochemistry to study the relationship between MHC II and plasma cell markers in DLBCL and plasmablastic lymphoma (PBL). Results demonstrate that MHC II(-) DLBCL immunophenotypically overlap with PBL and demonstrate an inverse correlation between MHC II and plasma cell markers MUM1, PRDM1/Blimp1, and XBP1s. In addition, MHC II expression is significantly higher in germinal center-DLBCL than activated B cell-DLBCL. A minor subset of cases with an unusual pattern of mislocalized punctate MHC II staining and intermediate levels of mRNA is also described. Finally, we show that PBL is negative for MHC II. The results imply a spectrum of MHC II expression that is more frequently diminished in tumors derived from B cells at the later stages of differentiation (with complete loss in PBL). Our observations provide a possible unifying concept that may contribute to the poor outcome reported in all MHC II(-) B-cell tumors.

Saglam A, Uner AH
Immunohistochemical expression of Mum-1, Oct-2 and Bcl-6 in systemic anaplastic large cell lymphomas.
Tumori. 2011 Sep-Oct; 97(5):634-8 [PubMed] Related Publications
AIMS AND BACKGROUND: Several transcription factors predominantly used for B-cell lineage identification are also expressed in a small percentage of T cells within germinal centers and interfollicular areas. The aim of the study was to evaluate the expression of Mum-1, Oct-2 and Bcl-6 in systemic anaplastic large cell lymphoma.
METHODS: Thirty cases of anaplastic large cell lymphoma were retrieved from our archives and tissue microarray constructed. Immunohistochemistry was carried out using an avidin-biotin peroxidase complex method.
RESULTS: A predominance of nuclear staining was observed for all transcription factors. Mum-1 was positive in all but one case (96.7%). Half of the cases displayed Oct-2 expression (15/30 cases). A considerable number of cases also had Bcl-6 expression (9/30). Bcl-6 staining was noted to be more common in ALK positive cases.
CONCLUSION: Our findings emphasize that these markers are not restricted to B-cell lineage and that extensive expression can be observed in anaplastic large cell lymphoma of T/null cell phenotype.

Yamazaki T, Ohno H
Double-hit lymphoma with t(8;14)(q24;q32) and t(12;14)(q24;q32) chromosomal translocations.
Intern Med. 2011; 50(21):2659-62 [PubMed] Related Publications
A 50-year-old man presented with an ileocecal tumor and a large amount of ascites. Lymphoma cells obtained from the ascitic fluid were CD10(+), CD20(+), CD38(+), HLA-DR(+), BCL6(-), MUM1/IRF4(+), BCL2(+), and immunoglobulin µ/γ(+). The karyotype determined by G-banding and spectral karyotyping was 46, XY, der(3)t(1;3)(q12;p12), -4, +7, t(8;14)(q24;q32), t(12;14)(q24;q32), der(17)t(4;17)(q21;p11). Fluorescence in situ hybridization disclosed that 93% of interphase cells were positive for the c-MYC and immunoglobulin heavy chain gene fusion. The patient was treated with intensive chemo-immunotherapy, resulting in a complete response. The t(8;14)-t(12;14) double-hit may have generated molecular abnormalities analogous to those of a previously cloned three-way translocation t(8;12;14).

Ozsan N, Bedke BJ, Law ME, et al.
Clinicopathologic and genetic characterization of follicular lymphomas presenting in the ovary reveals 2 distinct subgroups.
Am J Surg Pathol. 2011; 35(11):1691-9 [PubMed] Related Publications
Most lymphomas arising in the ovary are diffuse large B-cell or Burkitt lymphomas. Follicular lymphomas of the ovary are rare, and their clinicopathologic features are incompletely understood. We investigated clinical, morphologic, immunophenotypic, and genetic features of follicular lymphomas initially diagnosed in the ovary in 16 women. We performed immunohistochemistry for CD20, CD3, CD10, BCL6, IRF4/MUM1, and BCL2 and interphase fluorescence in situ hybridization for translocations involving BCL2, BCL6, and IRF4. Clustering was performed on the basis of clinicopathologic and genetic variables using Cluster 3.0. Ages ranged from 42 to 73 years. Unsupervised hierarchical clustering analysis revealed 2 distinct groups of patients. One group (group A) included 7 cases, which were negative or weakly positive for BCL2 protein and lacked IGH@/BCL2 translocations (6 cases evaluable). Four patients were of grade 3A, and 3 patients were of grade 2. Four had stage IE disease with unilateral ovarian involvement (subgroup A(1)), and the stage was unknown in 3 patients (subgroup A(2)). The second group (group B) included 9 cases of low histologic grade, which strongly expressed BCL2 protein and had IGH@/BCL2 translocations (7 cases evaluable). Six patients had stage III/IV disease, 2 had stage II disease, and the stage was unknown in 1 patient. Although follow-up intervals were limited, patients with higher-grade/low-stage disease tended to have favorable outcomes. These data indicate 2 distinct types of follicular lymphomas presenting in the ovary: a low-grade/high-stage/BCL2-positive group and a higher-grade/low-stage/BCL2-negative group. This latter group likely has distinct biological and immunologic characteristics, as has been suggested for higher-grade/low-stage follicular lymphomas presenting at other extranodal sites.

Thieblemont C, Briere J, Mounier N, et al.
The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study.
J Clin Oncol. 2011; 29(31):4079-87 [PubMed] Related Publications
PURPOSE: To evaluate the prognostic value of the cell of origin (COO) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBLC), prospectively treated by rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) versus rituximab, ifosfamide, carboplatin, and etoposide and followed by intensive therapy plus autologous stem-cell transplantation on the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) trial.
PATIENTS AND METHODS: Among the 396 patients included on the trial, histologic material was available for a total of 249 patients at diagnosis (n = 189 patients) and/or at relapse (n = 147 patients), which included 87 matched pairs. The patient data were analyzed by immunochemistry for CD10, BCL6, MUM1, FOXP1, and BCL2 expression and by fluorescent in situ hybridization for BCL2, BCL6 and c-MYC breakpoints. The correlation with survival data was performed by using the log-rank test and the Cox model.
RESULTS: Characteristics of immunophenotype and chromosomal abnormalities were statistically highly concordant in the matched biopsies. In univariate analysis, the presence of c-MYC gene rearrangement was the only parameter to be significantly correlated with a worse progression-free survival (PFS; P = .02) and a worse overall survival (P = .04). When treatment interaction was tested, the germinal center B (GCB) -like DLBCL that was based on the algorithm by Hans was significantly associated with a better PFS in the R-DHAP arm. In multivariate analysis, independent prognostic relevance was found for the GCB/non-GCB the Hans phenotype interaction treatment (P = .04), prior rituximab exposure (P = .0052), secondary age-adjusted International Prognostic Index (P = .039), and FoxP1 expression (P = .047). Confirmation was obtained by gene expression profiling in a subset of 39 patients.
CONCLUSION: COO remains a major and independent factor in relapsed/refractory DLBCL, with a better response to R-DHAP in GCB-like DLBCL. This needs confirmation by a prospective study.

Gadage V, Kembhavi S, Kumar P, Shet T
Primary cardiac diffuse large B-cell lymphoma with activated B-cell-like phenotype.
Indian J Pathol Microbiol. 2011 Jul-Sep; 54(3):591-3 [PubMed] Related Publications
Primary cardiac lymphoma (PCL) is a rare and fatal disorder. It may often mimic other common cardiac tumors like cardiac myxoma because of similarities in the clinical presentation. We report a case of PCL of diffuse large B-cell type, in a 38-year-old, immunocompetent male who presented with superior vena cava syndrome that was excised as a myxoma. Histology revealed a large cell population diffusely and strongly expressing CD45, CD20, MUM1/IRF4 and FOXP1 hinting at an activated B-cell (ABC)-like phenotype. After four cycles of Rituximab with CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) the tumor regressed completely but the patient had a relapse and subsequently succumbed to the disease confirming the aggressive nature. The aggressive behavior of PCL may be possibly linked to its ABC-like origin.

Ng SB, Yan J, Huang G, et al.
Dysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma.
Blood. 2011; 118(18):4919-29 [PubMed] Related Publications
We performed a comprehensive genome-wide miRNA expression profiling of extranodal nasal-type natural killer/T-cell lymphoma (NKTL) using formalin-fixed paraffin-embedded tissue (n = 30) and NK cell lines (n = 6) compared with normal NK cells, with the objective of understanding the pathogenetic role of miRNA deregulation in NKTL. Compared with normal NK cells, differentially expressed miRNAs in NKTL are predominantly down-regulated. Re-expression of down-regulated miRNAs, such as miR-101, miR-26a, miR26b, miR-28-5, and miR-363, reduced the growth of the NK cell line and modulated the expression of their predicted target genes, suggesting the potential functional role of the deregulated miRNAs in the oncogenesis of NKTL. Taken together, the predicted targets whose expression is inversely correlated with the expression of deregulated miRNA in NKTL are significantly enriched for genes involved in cell cycle-related, p53, and MAPK signaling pathways. We also performed immunohistochemical validation for selected target proteins and found overexpression of MUM1, BLIMP1, and STMN1 in NKTL, and notably, a corresponding increase in MYC expression. Because MYC is known to cause repression of miRNA expression, it is possible that MYC activation in NKTL may contribute to the suppression of the miRNAs regulating MUM1, BLIMP1, and STMN1.

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