A genomic and expression study of AP-1 in primary cutaneous T-cell lymphoma: evidence for dysregulated expression of JUNB and JUND in MF and SS.

Activator protein 1 (AP-1) consists of a group of transcription factors including the JUN and FOS family proteins with diverse biological functions. This study assessed the genomic and expression status of the AP-1 transcription factors in primary cutaneous T-cell lymphoma (CTCL) by using immunohistochemistry (IHC), Affymetrix expression microarray, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH). IHC showed JUNB protein expression in tumor cells from 17 of 33 cases of Sezary syndrome (SS) and JUND protein expression in 16 of 23 mycosis fungoides cases. There was no correlation between JUNB and CD30 expression. However, 7 of 12 JUNB-positive SS cases expressed both phosphorylated and total extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) proteins. Expression microarray showed over threefold increased expression of JUNB in three of six SS patients and similar findings were also noted after re-analysis of previously published data. Real-time RT-PCR confirmed the overexpression of JUNB in four SS cases and of JUND in three of four cases. FISH showed increased JUNB copy number in four of seven SS cases. These findings suggest that deregulation of AP-1 expression in CTCL is the result of aberrant expression of JUNB and possible JUND resulting from genomic amplification and constitutive activation of ERK1/2 MAPK in this type of lymphoma.