FOXP1 protein overexpression is associated with inferior outcome in nodal diffuse large B-cell lymphomas with non-germinal centre phenotype, independent of gains and structural aberrations at 3p14.1.
OBJECTIVE
To determine the molecular epidemiology and prognostic importance of structural and numeric FOXP1 gene aberrations with respect to BCL-6 gene and to FOXP1 protein expression in 389 diffuse large B-cell lymphomas (DLBCL) from the pre-rituximab era on tissue microarrays.


RESULTS
By interphase fluorescence in situ hybridization with colour-labelled bacterial artificial chromosome clones, 12% (27/223) analysable cases showed FOXP1 gains and 1% (2/210) FOXP1 breaks. Seven percent of cases with known BCL-6 and FOXP1 gene status (n = 159) showed an isolated FOXP1 gain, 19% an isolated BCL-6 gain and 18% a trisomy 3. FOXP1 gains (isolated and due to trisomy 3) were more frequent in nodal than extranodal DLBCL and in non-germinal centre B-cell-like (non-GCB) DLBCL than in GCB DLBCL. By immunohistochemistry, FOXP1 protein was more often overexpressed in non-GCB than in GCB cases. FOXP1 overexpression was associated with poor disease-specific survival in all DLBCL, particularly in nodal and non-GCB cases. There was no correlation between FOXP1 gene aberrations and either FOXP1 protein expression or survival.


CONCLUSIONS
FOXP1 is recurrently targeted by numeric, and rarely by structural, genetic aberrations in DLBCL. Only the presence of FOXP1 protein, irrespective of its gene status, is decisive for prognosis in DLBCL.
Hoeller
Sylvia
S
Institute of Pathology, University of Basel, Basel, Switzerland.
Schneider
Aurelia
A
Haralambieva
Eugenia
E
Dirnhofer
Stephan
S
Tzankov
Alexandar
A
D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins