Abstract
The angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in well-characterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34(+)CD105(+) endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34(+) endothelial cells, but not in CD3(+)CD10(+)lymphoma cells, or in CD34(+) endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34(+)CD105(+) neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105(+) neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antigens, CD / analysis*
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Antigens, CD34 / analysis
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Biomarkers, Tumor / analysis*
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Biomarkers, Tumor / genetics
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Case-Control Studies
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Chi-Square Distribution
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Disease Progression
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Disease-Free Survival
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Endoglin
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Endothelial Cells / chemistry*
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Endothelial Cells / immunology
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Endothelial Cells / pathology
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Female
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Fluorescent Antibody Technique
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Humans
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Immunoblastic Lymphadenopathy / genetics
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Immunoblastic Lymphadenopathy / immunology
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Immunoblastic Lymphadenopathy / metabolism*
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Immunoblastic Lymphadenopathy / mortality
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Immunoblastic Lymphadenopathy / pathology
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Immunoblastic Lymphadenopathy / therapy
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Kaplan-Meier Estimate
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Laser Capture Microdissection
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Lymph Nodes / blood supply
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Lymph Nodes / chemistry*
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphoma, T-Cell / chemistry*
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Lymphoma, T-Cell / genetics
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Lymphoma, T-Cell / immunology
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Lymphoma, T-Cell / mortality
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Lymphoma, T-Cell / pathology
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Lymphoma, T-Cell / therapy
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Male
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Microvessels / chemistry*
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Microvessels / immunology
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Microvessels / pathology
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Middle Aged
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Multivariate Analysis
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Neovascularization, Pathologic
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Paris
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Proportional Hazards Models
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Proto-Oncogene Proteins c-bcl-2 / analysis*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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RNA, Messenger / analysis
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Real-Time Polymerase Chain Reaction
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Receptors, Cell Surface / analysis*
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Risk Assessment
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Risk Factors
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Time Factors
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Treatment Outcome
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Tumor Microenvironment
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Vascular Endothelial Growth Factor A / analysis
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Vascular Endothelial Growth Factor A / genetics
Substances
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Antigens, CD
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Antigens, CD34
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Biomarkers, Tumor
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ENG protein, human
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Endoglin
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Receptors, Cell Surface
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VEGFA protein, human
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Vascular Endothelial Growth Factor A