Originally published as JCO Early Release 10.1200/JCO.2006.05.6150 on April 24 2006

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Forkhead Box Protein P1 Expression in Mucosa-Associated Lymphoid Tissue Lymphomas Predicts Poor Prognosis and Transformation to Diffuse Large B-Cell Lymphoma

Xavier Sagaert, Pascale de Paepe, Louis Libbrecht, Vera Vanhentenrijk, Gregor Verhoef, Jose Thomas, Iwona Wlodarska, Christiane De Wolf-Peeters

From the Departments of Morphology and Molecular Pathology, Hematology, and Oncology and the Centre for Human Genetics, Catholic University Leuven, Leuven; and Department of Pathology, Ghent University, Ghent, Belgium

Address reprint requests to Sagaert Xavier, MD, Department of Morphology and Molecular Pathology, Katholieke Universiteit Leuven, Minderbroederstraat 12, B-3000 Leuven, Belgium; e-mail: xavier.sagaert{at}uz.kuleuven.ac.be

PURPOSE: Gene expression profiling studies have reported upregulated mRNA expression of forkhead box protein P1 (FOXP1) in response to normal B-cell activation and high expression in a poor prognosis subtype of diffuse large B-cell lymphoma (DLBCL). Recently, it was also found that FOXP1 rearrangements and expression of its protein occur in mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we investigated FOXP1 expression in its relationship to morphology, genetic features, and prognosis in a series of 70 MALT lymphomas.

PATIENTS AND METHODS: All samples were morphologically reviewed and stained for FOXP1. Presence of structural and/or numeric aberrations of the FOXP1, BCL10, and MALT1 genes was investigated. For all patients, a complete clinical data set was collected.

RESULTS: We detected nuclear expression of FOXP1 in 20 of the 70 MALT lymphomas (nine of them featuring structural or numeric aberrations of the FOXP1 locus). FOXP1 positivity was confined to MALT lymphomas with poor clinical outcome (with impact of FOXP1 expression on relapse rate and disease-free survival). It was also found that MALT lymphomas with strong FOXP1 expression are at risk of transforming into an aggressive DLBCL of nongerminal center phenotype if they feature, in addition, a polymorphic histology and the presence of trisomy 3 and 18.

CONCLUSION: The data presented show that FOXP1 expression is an independent prognostic factor in MALT lymphomas. The data also support the hypothesis that a subgroup of nongerminal center DLBCLs (those marked by FOXP1 expression and trisomy 3 and 18) might represent a large-cell variant of MALT lymphomas.

Supported by Grant No. G.0362.01 from the Fund for Scientific Research (FWO) Flanders; X.S. and L.L. are research fellows of FWO Flanders; and V.V. is a research fellow of the Belgian Federation Against Cancer.

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

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