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Increased programmed death-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival

Muenst, Simone and Hoeller, Sylvia and Dirnhofer, Stephan and Tzankov, Alexandar. (2009) Increased programmed death-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival. Human pathology : a clinicopathologic quarterly, Vol. 40. pp. 1715-1722.

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Official URL: http://edoc.unibas.ch/dok/A6006183

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
UniBasel Contributors:Dirnhofer, Stephan and Tzankov, Alexandar
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:W.B. Saunders
ISSN:0046-8177
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:42

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