Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Sagaert
Xavier
X
Department of Morphology and Molecular Pathology, and the Centre for Human Genetics, Catholic University Leuven, Leuven, Belgium. xavier.sagaert@uz.kuleuven.ac.be
de Paepe
Pascale
P
Libbrecht
Louis
L
Vanhentenrijk
Vera
V
Verhoef
Gregor
G
Thomas
Jose
J
Wlodarska
Iwona
I
De Wolf-Peeters
Christiane
C
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012097:Repressor Proteins / Q000032:analysis* / Q000235:genetics*
D014408:Biomarkers, Tumor; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins