Published online 26 January 2008
Haematologica, Vol 93, Issue 2, 193-200 doi:10.3324/haematol.11702
Copyright © 2008 by Ferrata Storti Foundation
Alexandar Tzankov1, ,
Cecile Meier1 ,
Petra Hirschmann1 ,
Philip Went2 ,
Stefano A. Pileri3 ,
Stephan Dirnhofer1
Haematologica, Vol 93, Issue 2, 193-200 doi:10.3324/haematol.11702
Copyright © 2008 by Ferrata Storti Foundation
Malignant Lymphomas |
Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin’s lymphoma
1 Institute of Pathology, University Hospital Basel, Switzerland;
2 Institute of Pathology, Triemli Hospital, Zurich, Switzerland;
3 Chair of Pathology and Unit of Hematopathology, Institute of Hematology and Clinical Oncology "L. and A. Seràgnoli", University of Bologna, Italy
Correspondence: Alexandar Tzankov, MD, Department of Pathology, University Hospital Basel, Schoenbeinstr. 40, CH-4031 Basel, Switzerland. E-mail: atzankov{at}uhbs.ch
Background: The tumor microenvironment is important for the behavior of cancer. We assessed the distribution and biological significance of FOXP3+ regulatory T-cells (Treg) in lymphomas.
Design and Methods: The absolute number of intratumoral FOXP3+ cells was immunohistochemically studied on lymphoma tissue microarrays from 1019 cases of different types of lymphomas and correlated to phenotypic and clinical parameters in uni- and multivariate models. Receiver operating characteristic -curves were used to determine prognostic cut-off values of FOXP3+ cell density.
Results: Of the 1019 cases, 926 (91%) were evaluable. FOXP3+ cell density varied between the lymphoma entities, and was highest in follicular lymphoma. An increased number of tumor-infiltrating FOXP3+ cells over the receiver operating characteristic-determined cut-offs positively influenced both disease-specific and failure-free survival in follicular lymphoma (p=0.053) and disease-specific survival in germinal center-like diffuse large B-cell lymphoma (p=0.051) and overall and failure-free survival in classical Hodgkin’s lymphoma (p=0.004), but had a negative prognostic effect in non-germinal center diffuse large B-cell lymphoma (p=0.059). In a Cox regression model, considering stage and age, the amount of FOXP3+ cells was of independent prognostic significance for failure-free survival in classical Hodgkin’s lymphoma and of borderline significance for overall survival in classical Hodgkin’s lymphoma and disease-specific survival in germinal center-like and non-germinal center diffuse large B-cell lymphoma.
Conclusions: FOXP3+ cells represent important lymphoma/host microenvironment modulators. Assessment of FOXP3+ cell density can contribute to the prediction of outcome in diffuse large B-cell lymphoma, fallicular lymphoma and classical Hodgkin’s lymphoma.
Key words: lymphoma, Treg, FOXP3, tissue microarray, receiver operating characteristic curves.
Related Articles
Haematologica 2008 93: 207-214.
Haematologica 2008 93: 257-264.
This article has been cited by other articles:
 |
|
 |
|
  C. Steidl, T. Lee, S. P. Shah, P. Farinha, G. Han, T. Nayar, A. Delaney, S. J. Jones, J. Iqbal, D. D. Weisenburger, et al. Tumor-Associated Macrophages and Survival in Classic Hodgkin's Lymphoma N. Engl. J. Med., March 11, 2010; 362(10): 875 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Farinha, A. Al-Tourah, K. Gill, R. Klasa, J. M. Connors, and R. D. Gascoyne The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation Blood, January 14, 2010; 115(2): 289 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. GOLLUB, B. STASSEK, T. HUCKHAGEL, H.-W. BERND, M. KROKOWSKI, H. MERZ, A. C. FELLER, and C. THORNS BCL6-translocations Affect the Phenotype of Follicular Lymphomas Only in the Absence of t(14;18)IgH/BCL2 Anticancer Res, November 1, 2009; 29(11): 4649 - 4655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Adams, A Tzankov, A Lugli, and I Zlobec New time-dependent approach to analyse the prognostic significance of immunohistochemical biomarkers in colon cancer and diffuse large B-cell lymphoma J. Clin. Pathol., November 1, 2009; 62(11): 986 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Menetrier-Caux, M. Gobert, and C. Caux Differences in Tumor Regulatory T-Cell Localization and Activation Status Impact Patient Outcome Cancer Res., October 15, 2009; 69(20): 7895 - 7898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E C Obermann, M Csato, S Dirnhofer, and A Tzankov BCL2 gene aberration as an IPI-independent marker for poor outcome in non-germinal-centre diffuse large B cell lymphoma J. Clin. Pathol., October 1, 2009; 62(10): 903 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E C Obermann, M Csato, S Dirnhofer, and A Tzankov Aberrations of the MYC gene in unselected cases of diffuse large B-cell lymphoma are rare and unpredictable by morphological or immunohistochemical assessment J. Clin. Pathol., August 1, 2009; 62(8): 754 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chetaille, F. Bertucci, P. Finetti, B. Esterni, A. Stamatoullas, J. M. Picquenot, M. C. Copin, F. Morschhauser, O. Casasnovas, T. Petrella, et al. Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome Blood, March 19, 2009; 113(12): 2765 - 3775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mittal, N. A. Marshall, L. Duncan, D. J. Culligan, R. N. Barker, and M. A. Vickers Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma Blood, June 1, 2008; 111(11): 5359 - 5370. [Abstract] [Full Text] [PDF]
|
|