Document Detail


Increased programmed death-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival.
MedLine Citation:
PMID:  19695683     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Simone Muenst; Sylvia Hoeller; Stephan Dirnhofer; Alexandar Tzankov
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Publication Detail:
Type:  Journal Article     Date:  2009-08-19
Journal Detail:
Title:  Human pathology     Volume:  40     ISSN:  1532-8392     ISO Abbreviation:  Hum. Pathol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-16     Completed Date:  2009-12-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421547     Medline TA:  Hum Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1715-22     Citation Subset:  IM    
Affiliation:
Institute of Pathology, University of Basel, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
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:
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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