Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis

Lazzi, Stefano; Bellan, Cristiana; Onnis, Anna; Falco, Giulia De; Sayed, Shahin; Kostopoulos, Ioannis; Onorati, Monica; D’Amuri, Alessandro; Santopietro, Rosa; Vindigni, Carla; Fabbri, Alberto; Righi, Simona; Pileri, Stefano; Tosi, Piero; Leoncini, Lorenzo

doi:10.1016/j.humpath.2009.01.007

Cited by 26 publications

(28 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B-cell differentiation is regulated by PAX5, and therefore loss of this effector could allow T-cell antigen expression in B-cell neoplasms [31][32][33][34][35] ; however, most of our cases (with the exception of plasma cell neoplasms and 1 PBL) were positive for PAX5. This is in contrast to a recent report of lymphoid neoplasms with loss of PAX5 expression that coexpressed B-cell and T-cell antigens.…”

Section: Discussionmentioning

confidence: 64%

Clinicopathologic Features of B-Cell Lineage Neoplasms With Aberrant Expression of CD3

Oliveira

Grogg

Macon

et al. 2012

American Journal of Surgical Pathology

View full text Add to dashboard Cite

CD3 expression by immunohistochemistry was historically considered restricted to T-lineage or NK-lineage neoplasms but recently has been reported in rare cases of mature B-cell neoplasms, frequently in association with Epstein-Barr virus. Here, we describe the pathologic features of 21 B-cell lineage neoplasms that express CD3 protein by immunohistochemistry: 12 diffuse large B-cell lymphomas (DLBCLs); 2 plasmablastic lymphomas (PBLs); 4 plasma cell neoplasms; 2 Burkitt lymphomas; and 1 nodal follicular lymphoma, grade 3A. CD20 expression was negative or only partially positive in 13/21 cases. Epstein-Barr virus was positive in 3/20 tested cases (2 PBLs and 1 DLBCL). All tested neoplasms (14/14) had clonal immunoglobulin gene rearrangements, and no clonal T-cell gene rearrangements were detected (0/14). The 12 DLBCLs segregated into 2 main groups: 7 demonstrated features of plasmacytic differentiation but did not meet criteria for PBL, and 5 had anaplastic features. In addition to morphology, other features shared among the DLBCLs with plasmacytic differentiation, the plasma cell neoplasms, and the PBLs included extranodal presentation, cytoplasmic localization of CD3, and lack of expression of other T-cell antigens in most cases. In contrast, DLBCLs with anaplastic features and the single follicular lymphoma coexpressed multiple T-cell antigens in a predominantly membranous pattern and presented with nodal disease in a relatively younger patient population. Our data expand the spectrum of morphologic, phenotypic, and clinical features of B-cell neoplasms aberrantly expressing CD3. As these neoplasms often lack typical expression of B-cell antigens, knowledge of these features will help avoid misclassification.

show abstract

Section: Discussionmentioning

confidence: 64%

Clinicopathologic Features of B-Cell Lineage Neoplasms With Aberrant Expression of CD3

Oliveira

Grogg

Macon

et al. 2012

American Journal of Surgical Pathology

View full text Add to dashboard Cite

show abstract

“…Previous studies have identified that the PAX5 gene, which is located on chromosome 19p13 (Stapleton et al, 1993;Kovac et al, 2000), is associated frequently with chromosomal translocations (Busslinger et al, 1996). Aberrant PAX5 expression has been reported in several tumors (Baumann Kubetzko et al, 2004;Meza et al, 2006;Mhawech-Fauceglia et al, 2007;Lazzi et al, 2009), thus dysregulated expression of PAX5 is likely to be involved in carcinogenesis and the malignant progression of human cancers. A recent study demonstrated that the lack of expression of PAX5 in lymphoid neoplasms is associated with promoter hypermethylation, and cases with PAX5 silence were characterized by poor clinical outcome (Lazzi et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Aberrant PAX5 expression has been reported in several tumors (Baumann Kubetzko et al, 2004;Meza et al, 2006;Mhawech-Fauceglia et al, 2007;Lazzi et al, 2009), thus dysregulated expression of PAX5 is likely to be involved in carcinogenesis and the malignant progression of human cancers. A recent study demonstrated that the lack of expression of PAX5 in lymphoid neoplasms is associated with promoter hypermethylation, and cases with PAX5 silence were characterized by poor clinical outcome (Lazzi et al, 2009). In this study, we discovered that the frequent loss of PAX5 expression in GC is due to promoter methylation.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic inactivation of paired box gene 5, a novel tumor suppressor gene, through direct upregulation of p53 is associated with prognosis in gastric cancer patients

Cheung

et al. 2011

Oncogene

View full text Add to dashboard Cite

Using genome-wide methylation screening, we identified that paired box gene 5 (PAX5) is involved in human cancer development. However, the function of PAX5 in gastric cancer (GC) development is largely unclear. We analyzed its epigenetic inactivation, biological functions and clinical application in GC. PAX5 was silenced in seven out of eight GC cell lines. A significant downregulation was also detected in paired gastric tumors compared with adjacent non-cancerous tissues. The downregulation of PAX5 was closely linked to the promoter hypermethylation status and could be restored with demethylation treatment. Ectopic expression of PAX5 in silenced GC cell lines (AGS and BGC823) inhibited colony formation and cell viability, arrested cell cycle, induced apoptosis, suppressed cell migration and invasion and repressed tumorigenicity in nude mice. Consistent with the induction of apoptosis by PAX5 in vitro, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) staining showed significantly enhanced apoptotic cells in PAX5-expressed tumors compared with the vector control tumors. On the other hand, knockdown of PAX5 by PAX5-short hairpin RNA increased the cell viability and proliferation. The antitumorigenic function of PAX5 was revealed to be mediated by upregulating downstream targets of tumor protein 53 (p53), p21, BCL2-associated X protein, metastasis suppressor 1 and tissue inhibitors of metalloproteinase 1, and downregulating BCL2, cyclin D1, mesenchymal-epithelial transition factor (MET) and matrix metalloproteinase 1. Immunoprecipitation assay demonstrated that PAX5 directly bound to the promoters of p53 and MET. Moreover, PAX5 hypermethylation was detected in 77% (144 of 187) of primary GCs compared with 10.5% (2/19) of normal gastric tissues (Po0.0001).GC patients with PAX5 methylation had a significant poor survival compared with the unmethylated cases as demonstrated by Cox regression model and log-rank test.In conclusion, PAX5 is a novel functional tumor suppressor in gastric carcinogenesis. Detection of methylated PAX5 can be utilized as an independent prognostic factor in GC.

show abstract

“…135 Rare cases of composite cutaneous B-cell and T-cell lymphomas cited in literature include MF with CLL/small lymphocytic lymphoma, 136 MF with MZL, 136 methotrexate-associated composite lymphoma of MF with FCL, 137 and EBV-associated DLBCL with PTL. 138 Two cases of primary cutaneous composite T-cell and B-cell lymphomas with morphological atypical populations of both lineages, but not classifiable in distinct subtypes, have been reported 129,139 (Table 6). It is important that a composite lymphoma of B cell and T-cell is to be distinguished from the dual genotype in a single lymphoma.…”

Section: Composite Lymphomasmentioning

confidence: 99%

Pitfalls in the Diagnosis of Cutaneous Lymphoma

Batrani

Bhawan

2014

The American Journal of Dermatopathology

View full text Add to dashboard Cite

Cutaneous lymphomas are primarily classified as cutaneous T-cell/natural killer (NK) cell lymphomas and B-cell lymphomas; their classification being of utmost importance for prognostic and therapeutic purposes. Despite certain distinguishing attributes related to both these categories of lymphomas, considerable overlaps and deviations from the usual features exist and can lead to misclassification. The objective of this review is to discuss the various pitfalls involving morphology, immunohistochemistry, and gene rearrangement studies, all of which pose challenges in classifying cutaneous lymphomas as either the T-cell/natural killer cell or B-cell type.

show abstract

Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis

Cited by 26 publications

References 43 publications

Clinicopathologic Features of B-Cell Lineage Neoplasms With Aberrant Expression of CD3

Clinicopathologic Features of B-Cell Lineage Neoplasms With Aberrant Expression of CD3

Epigenetic inactivation of paired box gene 5, a novel tumor suppressor gene, through direct upregulation of p53 is associated with prognosis in gastric cancer patients

Pitfalls in the Diagnosis of Cutaneous Lymphoma

Contact Info

Product

Resources

About