| Increased programmed death-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival. | |
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MedLine Citation:
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PMID: 19695683 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Programmed death-1 (PD-1), a protein that is physiologically expressed by germinal center-associated helper T cells, has an inhibitory function on T-cell activity. The distribution of PD-1+ lymphocytes in the microenvironment of Hodgkin lymphoma is not random and can serve as a diagnostic marker. We measured the number of PD-1+ lymphocytes in Hodgkin lymphoma and correlated it with the remaining background lymphocyte populations and known biological and clinical key data on a tissue microarray platform encompassing 280 cases of classical Hodgkin lymphoma and 3 cases of nodular lymphocyte-predominant Hodgkin lymphoma. Prognostic cutoff scores were determined by receiver operating curve analysis. The number of PD-1+ tumor-infiltrating lymphocytes in 189 evaluable cases was median of 27 and mean of 269 cells/mm(2), being higher in lymphocyte-rich classical Hodgkin lymphoma and lower in the mixed cellularity variant. Rimming of tumor cells by PD-1+ cells was observed in all cases of nodular lymphocyte-predominant Hodgkin lymphoma but only in 1% of classical Hodgkin lymphomas, particularly in lymphocyte-rich and -mixed cellularity variants. Thus, the presence of PD-1+ rosettes around neoplastic cells is typical but not exclusive for nodular lymphocyte-predominant Hodgkin lymphoma because it may be encountered in classical Hodgkin lymphoma. The PD-1+ cell amount was lower in classical Hodgkin lymphoma cases with 9p24 gains (PD-1 ligand 2 locus) and in cases with higher numbers of FOXP3+ regulatory T cells. An increased amount of PD-1+ tumor-infiltrating lymphocytes above the prognostic cutoff score (23 cells/mm(2)) was a stage-independent negative prognostic factor of overall survival as opposed to the number of FOXP3+ regulatory T cells. Along with the latter, PD-1+ cells might represent important lymphoma/host microenvironment modulators. |
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Authors:
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Simone Muenst; Sylvia Hoeller; Stephan Dirnhofer; Alexandar Tzankov |
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Publication Detail:
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Type: Journal Article Date: 2009-08-19 |
Journal Detail:
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Title: Human pathology Volume: 40 ISSN: 1532-8392 ISO Abbreviation: Hum. Pathol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-16 Completed Date: 2009-12-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421547 Medline TA: Hum Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1715-22 Citation Subset: IM |
Affiliation:
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Institute of Pathology, University of Basel, Basel, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antigens, CD / biosynthesis*, immunology Apoptosis Regulatory Proteins / biosynthesis*, immunology Area Under Curve Female Forkhead Transcription Factors / biosynthesis, immunology Hodgkin Disease / immunology*, metabolism, mortality Humans Kaplan-Meiers Estimate Lymphocytes, Tumor-Infiltrating / immunology*, metabolism Male Middle Aged Neoplasm Staging Prognosis ROC Curve T-Lymphocytes, Helper-Inducer / immunology*, metabolism T-Lymphocytes, Regulatory / immunology, metabolism Tissue Array Analysis Tumor Markers, Biological / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Apoptosis Regulatory Proteins; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Tumor Markers, Biological; 146588-21-8/PDCD1 protein, human |
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