Originally published as JCO Early Release 10.1200/JCO.2006.06.1648 on January 2 2007

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Gene-Expression and Immunohistochemical Study of Specific T-Cell Subsets and Accessory Cell Types in the Transformation and Prognosis of Follicular Lymphoma

Annuska M. Glas, Laurent Knoops, Leonie Delahaye, Marie José Kersten, Robby E. Kibbelaar, Lodewyk A. Wessels, Ryan van Laar, J. Han J.M. van Krieken, Joke W. Baars, John Raemaekers, Philip M. Kluin, Laura J. van ’t Veer, Daphne de Jong

From the Departments of Pathology and Medical Oncology/Hematology, the Netherlands Cancer Institute; Agendia BV; Department of Hematology, Academic Medical Center, Amsterdam, the Netherlands; Department of Pathology, Central Laboratories, Friesland; Department of Pathology, Radboud University Medical Center Nijmegen; Department of Hematology, Radboud University Medical Center Nijmegen, Nijmegen; Department of Pathology, University Medical Center Groningen, Groningen, the Netherlands; and the Experimental Medicine Unit, Université Catholique de Louvain, Belgium

Address reprint requests to Daphne de Jong, Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; e-mail: d.d.jong{at}nki.nl

Purpose Despite the generally favorable clinical course in follicular lymphoma (FL), a minority of patients have a poor prognosis—with death within 3 years of diagnosis—most often due to transformation to aggressive disease.

Patients and Methods In this study, we analyzed the potential of predicting early transformation on the basis of gene expression and immunologic parameters in FL biopsy samples taken at diagnosis.

Results At the gene-expression level, FL is a highly uniform disease at the time of diagnosis, precluding the detection of sufficiently validated prognostic gene-expression profiles suitable for a clinical setting. Combinations of differentially expressed genes indicate that immunologic mechanisms play a differential role in the risk of early transformation. Using immunohistochemistry for specific cell populations, the spatial distribution to neoplastic follicles and the activation of CD4–positive T-helper cells (P = .002) and specifically T-helper 1 (P = .004) were shown to be highly discriminatory to predict early transformation. A role for functional modulation of follicular dendritic cells could also be supported (P = .04). Other cell populations, including CD68-positive macrophages and regulatory T cells, were not differentially present.

Conclusion These results support the identification of FL as an immunologically functional disease in which an interaction of the tumor cells and the functional composition of the microenvironment determines the clinical behavior.

published online ahead of print at www.jco.org on January 2, 2007.

Supported by a grant from the Belgian Federation Against Cancer (L.K.).

A.M.G. and L.K. contributed equally to this study.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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